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{{Short description|CNS stimulant and isomer of amphetamine}}
{{Use dmy dates|date=July 2013}}
<noinclude>{{Requested move notice|1=Dexamfetamine|2=Talk:Dextroamphetamine#Requested move 4 January 2025}}
{{inadequate lead|date=January 2014}}
</noinclude>{{Use dmy dates|date=December 2023}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
| IUPAC_name = (2S)-1-phenylpropan-2-amine
{{Infobox drug
| image = Dexamfetamine2DACS.svg
| Verifiedfields = changed
| width = 150
| Watchedfields = changed
| image2 = Dexamfetamine3Dan.gif
| verifiedrevid = 596899008
| width2 = 175
| INN = Dexamfetamine
<!-- Clinical data -->
| image = D-amphetamine.svg
| tradename = Dexedrine, Dextrostat, Dexamphetamine
| width = 210
| alt =
| imageL = D-Amphetamine-3D-balls.png
| altL =
| imageR = Amphetamine-3d-CPK.png
| altR =
| caption = <!-- Clinical data -->
| pronounce = {{IPAc-en|ˌ|d|ɛ|k|s|t|r|əʊ|æ|m|ˈ|f|ɛ|t|ə|m|iː|n}}
| tradename = Dexedrine, others
| Drugs.com = {{drugs.com|monograph|dextroamphetamine}} | Drugs.com = {{drugs.com|monograph|dextroamphetamine}}
| MedlinePlus = a605027 | MedlinePlus = a605027
| DailyMedID = Dextroamphetamine
| licence_EU =
| licence_US = Dextroamphetamine Sulfate
| DailyMedID = ec2d13f3-d14f-47e4-abe9-7763f95a8e94
| pregnancy_AU = B3 | pregnancy_AU = B3
| pregnancy_AU_comment =
| pregnancy_US = C
| pregnancy_category =
| dependency_liability = Moderate<ref name="Vitiello2008">{{cite journal | vauthors = Vitiello B | title = Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function | journal = Child and Adolescent Psychiatric Clinics of North America | volume = 17 | issue = 2 | pages = 459–74, xi | date = April 2008 | pmid = 18295156 | pmc = 2408826 | doi = 10.1016/j.chc.2007.11.010 }}</ref><ref name="GrahamGrahamBanaschewski2010">{{cite journal | vauthors = Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M, Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A, Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong IC, Zuddas A, Steinhausen HC, Taylor E | title = European guidelines on managing adverse effects of medication for ADHD | journal = European Child & Adolescent Psychiatry | volume = 20 | issue = 1 | pages = 17–37 | date = January 2011 | pmid = 21042924 | pmc = 3012210 | doi = 10.1007/s00787-010-0140-6 | eissn = 1435-165X }}</ref> – high<ref name="KociancicReedFindling2004">{{cite journal | vauthors = Kociancic T, Reed MD, Findling RL | title = Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children | journal = Expert Opinion on Drug Safety | volume = 3 | issue = 2 | pages = 93–100 | date = March 2004 | pmid = 15006715 | doi = 10.1517/14740338.3.2.93 | s2cid = 31114829 | eissn = 1744-764X }}</ref><ref name="ClemowWalker2014">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 | eissn = 1941-9260 }}</ref><ref name="Stahl's Essential Psychopharmacology" />
| addiction_liability = Moderate<ref name="Vitiello2008"/><ref name="GrahamGrahamBanaschewski2010"/> – high<ref name="KociancicReedFindling2004"/><ref name="ClemowWalker2014"/><ref name="Stahl's Essential Psychopharmacology" />
| routes_of_administration = ], ]
| class = ]
| ATC_prefix = N06
| ATC_suffix = BA02
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S8 | legal_AU = S8
| legal_AU_comment = <ref>{{cite web | title=Therapeutic Goods (Poisons Standard—February 2023) Instrument 2022 | website=Australian Government Federal Register of Legislation | date=26 September 2022 | url=https://www.legislation.gov.au/Series/F2022L01257 | access-date=9 January 2023}}</ref><ref>{{cite web | vauthors = Fuller K | title=ADHD Stimulant Prescribing Regulations & Authorities in Australia & New Zealand | website=AADPA | date=20 February 2022 | url=https://aadpa.com.au/adhd-stimulant-prescribing-regulations-in-australia-new-zealand/ | access-date=9 January 2023}}</ref>
| legal_CA = Schedule I
| legal_BR = A3
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = /{{nbsp}}Schedule G (CDSA I)<ref>{{cite web | title=Product monograph brand safety updates | website=] | date=6 June 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=8 June 2024}}</ref>
| legal_DE = Anlage III
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = Class B | legal_UK = Class B
| legal_UK_comment =
| legal_US = Schedule II | legal_US = Schedule II
| legal_US_comment = <ref name="Dexedrine FDA label">{{cite web | title=Dexedrine spansule- dextroamphetamine sulfate capsule, extended release | website=DailyMed | date=10 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc717b9b-22ea-4c60-a1d4-ee38a40bce78 | access-date=28 March 2022}}</ref><ref name="Xelstrym FDA label">{{cite web | title=Xelstrym- dextroamphetamine patch, extended release | website=DailyMed | date=6 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0862f02a-72a8-41cc-8845-57cf4974bb6f | access-date=21 January 2023}}</ref>
| dependency_liability = Moderate to High
| legal_EU = Rx-only
| routes_of_administration = Oral (only medically-utilized route)
| legal_EU_comment = <ref>{{cite web|url=https://www.ema.europa.eu/documents/psusa/dexamfetamine-list-nationally-authorised-medicinal-products-psusa/00000986/202109_en.pdf |title=List of nationally authorised medicinal products : Active substance(s): dexamfetamine : Procedure No. PSUSA/00000986/202109|website=Ema.europa.eu|access-date=5 June 2022}}</ref>
<!-- Pharmacokinetic data -->
| legal_UN = P II
| bioavailability = Oral 75&ndash;100%<ref>{{cite web | title=Dextromphetamine | url=http://www.drugbank.ca/drugs/DB01576#pharmacology | work=DrugBank | accessdate=5 November 2013 | section=Pharmacology }}</ref>
| protein_bound = | legal_UN_comment =
| legal_status = SE: Förteckning II
| metabolism = ]: ],<ref name="FDA Pharmacokinetics">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | pages = 12&ndash;13 | work = United States Food and Drug Administration |date=December 2013 | accessdate = 30 December 2013 }}</ref> ],<ref name="DBH ref">{{cite book | title=Foye's Principles of Medicinal Chemistry | year=2013 | publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins | location=Philadelphia | isbn=1609133455 | page=648 | author=Lemke TL, Williams DA, Roche VF, Zito W|edition=7th ed. | quote=Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.}}</ref> and ]<ref name="FMO">{{cite journal | author = Krueger SK, Williams DE | title = Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism | journal = Pharmacol. Ther. | volume = 106 | issue = 3 | pages = 357&ndash;387 |date=June 2005 | pmid = 15922018 | pmc = 1828602 | doi = 10.1016/j.pharmthera.2005.01.001 }}</ref>

| elimination_half-life = 10-12 hours<ref name = TGA>{{cite web | title = Dexedrine Medication Guide | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017078s046lbl.pdf | work = United States Food and Drug Administration |date=May 2013 | accessdate = 2 November 2013 | page = 1 }}</ref><ref>{{cite web|title=Dextroamphetamine Sulfate (dextroamphetamine sulfate) Tablet |work=DailyMed|publisher=ETHEX Corporation|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bed3c03f4-2829-423f-a595-dc09c9cc0e40|date=February 2008|accessdate=8 November 2013}}</ref>
<!-- Pharmacokinetic data -->| bioavailability = Oral: ~90%<ref name="handbook2022" />
| excretion = Renal (45%);<ref>{{cite web|title=dextrostat (dextroamphetamine sulfate) tablet |publisher=Shire US Inc.|work=DailyMed|url=http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=1645|date=August 2006|accessdate=8 November 2013|location=Wayne, PA}}</ref> urinary pH-dependent
| protein_bound = 15–40%<ref name="Drugbank-amph" />
<!-- Identifiers -->
| metabolism = ],<ref name="FDA Pharmacokinetics" /> ],<ref name="DBH ref">{{cite book | title=Foye's Principles of Medicinal Chemistry | year=2013 | publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins | location=Philadelphia | isbn=978-1-60913-345-0 | page=648 |vauthors=Lemke TL, Williams DA, Roche VF, Zito W |edition=7th | quote=Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.}}</ref> ]<ref name="FMO" />
| metabolites =
| onset = {{abbr|IR|Immediate release}} dosing: 0.5–1.5&nbsp;hours<ref>{{Cite book|title = Primary Care Pediatrics|url = https://books.google.com/books?id=o43u_qWT4asC|publisher = Lippincott Williams & Wilkins|date = 1 January 2001|isbn = 978-0-7817-2008-3| vauthors = Green-Hernandez C, Singleton JK, Aronzon DZ |page = 243}}|quote = Table 21.2 Medications for ADHD ... D-amphetamine ... Onset: 30 min.</ref><ref>{{cite web|title = Dexedrine, ProCentra(dextroamphetamine) dosing, indications, interactions, adverse effects, and more|url = http://reference.medscape.com/drug/dexedrine-procentra-dextroamphetamine-342998#10|website = reference.medscape.com|access-date = 4 October 2015|quote = Onset of action: 1–1.5 hr}}</ref><br />{{abbr|XR|Extended release}} dosing: 1.5–2&nbsp;hours<ref name="Millichap: onset, peak, and duration">{{cite book | vauthors = Millichap JG | editor = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, USA | isbn = 978-1-4419-1396-8 | page = 112 | edition = 2nd | chapter = Chapter 9: Medications for ADHD | quote = <br />Table 9.2 Dextroamphetamine formulations of stimulant medication<br />Dexedrine &nbsp;...<br />Adderall <br />Dexedrine spansules &nbsp;...<br />Adderall XR <br />Vyvanse }}</ref><ref name="XR onset-duration">{{cite journal | vauthors = Brams M, Mao AR, Doyle RL | title = Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder | journal = Postgrad. Med. | volume = 120 | issue = 3 | pages = 69–88 | date = September 2008 | pmid = 18824827 | doi = 10.3810/pgm.2008.09.1909 | s2cid = 31791162 | quote = Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours.&nbsp;... MAS-XR, and LDX have a long duration of action at 12 hours postdose}}</ref>
| elimination_half-life = 9–11&nbsp;hours<ref name="FDA Pharmacokinetics" /><ref name="Adderall IR">{{cite web | title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet | website=DailyMed | date=27 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 | access-date=21 January 2023}}</ref><br />]-dependent: 7–34&nbsp;hours<ref name="HSDB Toxnet October 2017 Full archived record" />
| duration_of_action = {{abbr|IR|Immediate release}} dosing: 3–6&nbsp;hours<ref name="Millichap: onset, peak, and duration" /><ref name="Narcolepsy guide2">{{cite journal | vauthors = Mignot EJ | title = A practical guide to the therapy of narcolepsy and hypersomnia syndromes | journal = Neurotherapeutics | volume = 9 | issue = 4 | pages = 739–752 | date = October 2012 | pmid = 23065655 | pmc = 3480574 | doi = 10.1007/s13311-012-0150-9}}</ref><br />{{abbr|XR|Extended release}} dosing: 8–12&nbsp;hours<ref name="Stahl's Essential Psychopharmacology - dextroamphetamine">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=March 2017 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=978-1-108-22874-9 | pages=39–44 | edition=6th | chapter-url=https://books.google.com/books?id=9hssDwAAQBAJ&pg=PA39 | chapter=Amphetamine (D) | access-date=8 August 2017}}</ref><ref name="Millichap: onset, peak, and duration" /><ref name="Narcolepsy guide2"/>
| excretion = ] (45%);<ref>{{cite web|title=dextrostat (dextroamphetamine sulfate) tablet |publisher=Shire US Inc.|website=DailyMed|url=http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=1645|date=August 2006|access-date=8 November 2013|location=Wayne, PA}}</ref>{{failed verification|date=December 2024}} urinary pH-dependent

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 51-64-9 | CAS_number = 51-64-9
| ATC_prefix = N06 | CAS_supplemental =
| ATC_suffix = BA02
| ATC_supplemental =
| PubChem = 5826 | PubChem = 5826
| IUPHAR_ligand = | IUPHAR_ligand = 2147
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01576 | DrugBank = DB01576
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5621 | ChemSpiderID = 5621
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = TZ47U051FI | UNII = TZ47U051FI
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03740 | KEGG = D03740
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4469 | ChEBI = 4469
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 612 | ChEMBL = 612
| synonyms = | NIAID_ChemDB =
| PDB_ligand =
<!-- Chemical data -->
| synonyms = d-Amphetamine, (S)-Amphetamine, S(+)-Amphetamine
| chemical_formula =

| C=9 | H=13 | Ag= | As= | Au= | B= | Bi= | Br= | Cl= | Co= | F= | Fe= | Gd= | I=
<!-- Chemical and physical data -->| IUPAC_name = (2''S'')-1-Phenylpropan-2-amine
| K= | Mn= | N=1 | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge=
| C = 9
| molecular_weight = 135.20622
| H = 13
| smiles = C(N)CC1=CC=CC=C1
| N = 1
| StdInChI = 1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
| chirality = ] ]
| StdInChI_comment =
| SMILES = C(Cc1ccccc1)N
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KWTSXDURSIMDCE-QMMMGPOBSA-N | StdInChIKey = KWTSXDURSIMDCE-QMMMGPOBSA-N
| density = 0.913 | density = 0.913
| melting_point = | density_notes =
| melting_notes = | melting_point =
| melting_high =
| melting_notes =
| boiling_point = 201.5 | boiling_point = 201.5
| boiling_notes = | boiling_notes =
| solubility = 20 | solubility = 20
| sol_units =
| specific_rotation =
}} }}


'''Dextroamphetamine''' (]: '''dexamfetamine''') is a potent ] (CNS) ] and ]<ref name="Enantiomer" group="note" /> of ] that is primarily prescribed for the treatment of ] (ADHD) and ].<ref name="Dexedrine FDA label" /><ref name="Amph Uses" /> It has also been used illicitly to enhance ] and athletic ], as well as an ] and ]. Dextroamphetamine is generally regarded as the ] ].
'''Dextroamphetamine''' (]), '''Dexamphetamine''' (])<ref name = AMH>{{cite isbn|9780980579093}}</ref><ref name = APF>{{cite isbn|9780646570198|chapter=Section D: Clinical monographs of commonly used medicines|page=291}}</ref> and '''Dexamfetamine''' (] and ]) is a potent ] and ] ] prescribed for the treatment of ] (ADHD) in children and adults as well as for a sleep disorder known as ]. Dextroamphetamine is also widely used by military air forces as a 'go-pill' during fatigue-inducing mission profiles such as night-time bombing missions.

The amphetamine molecule exists as two enantiomers,{{#tag:ref|Enantiomers are molecules that are mirror images of one another; they are structurally identical, but of the opposite orientation.<ref name="Enantiomers">{{GoldBookRef |title=enantiomer |file=E02069 }}</ref>|group = "note" |name="Enantiomer"}} ] and dextroamphetamine. Dextroamphetamine is the ], or 'right-handed', enantiomer and exhibits more pronounced effects on the central nervous system than levoamphetamine. Pharmaceutical dextroamphetamine sulfate is available as both a ] and ] in a variety of ]s. Dextroamphetamine is sometimes prescribed as the ] ], which is converted into dextroamphetamine after absorption.

Side effects of dextroamphetamine at therapeutic doses include ], ], ], ], ], ], increased ] or ], ], and ], among others.<ref name="AHFS2019" /> At excessively high doses, ] (i.e., ]s, ]s), ], and ] may occur. However, for individuals with pre-existing psychotic disorders, there may be a risk of psychosis even at therapeutic doses.<ref name="Adderall XR FDA label" />


Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or ] for the ] neurotransmitters (namely the ], ] and ]s) either via ] (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters<ref name=Miller/> and it releases these neurotransmitters from ] via ].<ref name="E Weihe" /> It also shares many chemical and pharmacological properties with human ]s, particularly ] and {{nowrap|]}}, the latter being an ] of amphetamine produced within the human body. It is available as a ].<ref name=AHFS2019>{{cite web |title=Dextroamphetamine Monograph for Professionals |url=https://www.drugs.com/monograph/dextroamphetamine.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=2 February 2019 |archive-date=3 February 2019 |archive-url=https://web.archive.org/web/20190203030724/https://www.drugs.com/monograph/dextroamphetamine.html |url-status=live }}</ref> In 2022, ] (Adderall) was the 14th most commonly prescribed medication in the United States, with more than 34{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Dextroamphetamine; Dextroamphetamine Saccharate; Amphetamine; Amphetamine Aspartate Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DextroamphetamineDextroamphetamineSaccharateAmphetamineAmphetamineAspartate | access-date = 30 August 2024 }}</ref>
The amphetamine molecule has two stereoisomers: ] and dextroamphetamine. Dextroamphetamine is the ], or ''"right-handed"'', ] of the ] molecule. Dextroamphetamine is available as a ] or under several brand names, including Dexedrine and Dextrostat, Dexamphetamine. Dextroamphetamine is also an active metabolite of the ] ].
{{TOC limit|3}}


==Uses== ==Uses==
{{More information|Amphetamine#Uses}}


===Medical=== ===Medical===
] ]
Dextroamphetamine is used to treat ] (ADHD) and ] (a ]),<ref name="Dexedrine FDA label" /> and is sometimes prescribed {{nowrap|]}} for ] and ].<ref name="Amph Uses" />
Dextroamphetamine is used for the treatment of ] and ].<ref>First line treatments </ref>
====ADHD====
Dextroamphetamine may be used under circumstances other than (indicated) for off-label use in the following conditions:
<!-- PLEASE NOTE: the following content is transcluded from its parent article ]. If you wish to alter content on ADHD, then go to ] and edit the source code there. After you finalise your edit, it will render here accordingly -->
* ]
{{#lsth:Amphetamine|ADHD}}
* ]
* ]
* Developmental disabilities
* ] recovery


====Investigational uses==== ====Narcolepsy====
<!-- PLEASE NOTE: the following content is transcluded from its parent article ]. If you wish to alter content on narcolepsy, then go to ] and edit the source code there. After you finalise your edit, it will render here accordingly -->
Though such use remains out of the mainstream, dextroamphetamine has been successfully applied in the treatment of certain categories of depression as well as other psychiatric syndromes.<ref>{{Cite journal|author = Warneke L|title = Psychostimulants in psychiatry|journal = Can J Psychiatry|volume = 35|issue = 1|pages = 3–10|year = 1990|pmid = 2180548}}</ref>
{{#lsth:Amphetamine|Narcolepsy}}
Such alternate uses include reduction of ],<ref>{{Cite journal|author = Breitbart W, Alici Y|title = Psychostimulants for cancer-related fatigue.|journal = J Natl Compr Canc Netw|volume = 8|issue = 8|pages = 933–42|year = 2010|pmid = 20870637}}</ref> antidepressant treatment for ] patients with depression and debilitating fatigue,<ref>{{Cite journal|doi = 10.4088/JCP.v61n0608|author = Wagner G, Rabkin R|title = Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial|journal = J Clin Psychiatry|volume = 61|issue = 6|pages = 436–40|year = 2000|pmid = 10901342}}</ref> and early-stage physiotherapy for severe stroke victims.<ref>{{Cite journal|author = Martinsson L, Yang X, Beck O, Wahlgren N, Eksborg S|title = Pharmacokinetics of dextroamphetamine in acute stroke|journal = Clin Neuropharmacol|volume = 26|issue = 5|pages = 270–6|year = 2003|pmid = 14520168|doi = 10.1097/00002826-200309000-00012}}</ref>
If ] patients take dextroamphetamine while they practice their movements for rehabilitation, they may learn to move much faster than without dextroamphetamine, and in practice sessions with shorter lengths.<ref name = "Butefisch">{{Cite journal|author = Butefisch CM ''et al.''|title = Modulation of Use-Dependent Plasticity by D-Amphetamine|journal = Annals of Neurology|volume = 51|issue = 1|pages = 59–68|year = 2002|pmid = 11782985|doi = 10.1002/ana.10056|first2 = Benjamin C.|first3 = Lumy|first4 = Daniel|first5 = Joseph|first6 = Leonid|first7 = Leonardo G.}}</ref>


===Enhancing performance===
==Contraindications==
{{transcluded section|source=Amphetamine}}
''Sources''<ref name = TGA/><ref name = DM>{{cite web|title=DEXTROAMPHETAMINE SULFATE tablet |work=DailyMed|publisher=Barr Laboratories Inc.|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ec2d13f3-d14f-47e4-abe9-7763f95a8e94|date=October 2013|accessdate=7 November 2013}}</ref><ref name = MS>{{cite web|title=dextroamphetamine (Rx) - Dexedrine, Liquadd, more...|accessdate=7 November 2013|url=http://reference.medscape.com/drug/dexedrine-liquadd-dextroamphetamine-342998|work=Medscape Reference|publisher=WebMD}}</ref>
{{trim|{{#section-h:Amphetamine|Enhancing performance}}}}
* ]
* Moderate-severe ]
* ]
* ]
* ]
* ]
* ]
* Advanced ]
* ]
* Angina pectoris
* ] or ] to the ] ]
* During or within 14 days following the administration of ] (MAOIs) (] may occur)<ref name = TGA/><ref name = DM/><ref name = MS/><ref></ref>


==Side effects== ===Recreational===
Dextroamphetamine is also used recreationally as a euphoriant and aphrodisiac, and, like other ], is used as a ] for its energetic and euphoric high. Dextroamphetamine is considered to have a high potential for misuse in a ] since individuals typically report feeling ], more alert, and more energetic after taking the drug.<ref>{{cite web|url=http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart |title=Commonly Abused Prescription Drugs Chart |publisher=National Institute on Drug Abuse|access-date=7 May 2012}}</ref><ref>{{cite web |url=http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |title=Stimulant ADHD Medications – Methylphenidate and Amphetamines |publisher=National Institute on Drug Abuse |access-date=7 May 2012 |archive-date=2 May 2012 |archive-url=https://web.archive.org/web/20120502072325/http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |url-status=dead }}</ref><ref name="NIDA ADHD stimulants" /> Dextroamphetamine's ] (rewarding) properties affect the ]; a group of neural structures responsible for ] (i.e., "wanting"; desire or craving for a reward and motivation), ] and ] emotions, particularly ones involving ].<ref name=Schultz>{{cite journal | vauthors = Schultz W | year = 2015 | title = Neuronal reward and decision signals: from theories to data | journal = Physiological Reviews | volume = 95 | issue = 3 | pages = 853–951 | pmid = 26109341 | pmc = 4491543 | doi=10.1152/physrev.00023.2014 | quote = Rewards in operant conditioning are positive reinforcers.&nbsp;... Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of several reward functions.&nbsp;... Rewards are attractive. They are motivating and make us exert an effort.&nbsp;... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior.&nbsp;... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward.&nbsp;... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory)&nbsp;... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses. The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning)&nbsp;... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components. This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism's survival and reproduction, whereas all other components are only supportive of these functions.&nbsp;... Rewards can also be intrinsic to behavior. They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards.&nbsp;... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward.&nbsp;... These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research and strongly support the learning and approach generating functions of reward.}}</ref> Large recreational doses of dextroamphetamine may produce ].<ref name="NIDA ADHD stimulants" /> Recreational users sometimes open dexedrine capsules and crush the contents in order to insufflate (snort) it or subsequently dissolve it in water and inject it.<ref name="NIDA ADHD stimulants">{{cite web|title=National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines|url=http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines|publisher=National Institute on Drug Abuse|access-date=27 February 2013}}</ref> Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to a more favorable pharmacokinetic profile and easy crushability (especially tablets).<ref name="CADDRA_2018">{{cite book |title=Canadian ADHD Practice Guidelines |date=2018 |publisher=Canadian ADHD Resource Alliance |page=67 |edition=Fourth |url=https://www.caddra.ca/wp-content/uploads/CADDRA-Guidelines-4th-Edition_-Feb2018.pdf |access-date=2 May 2023 |archive-date=2 May 2023 |archive-url=https://web.archive.org/web/20230502204112/https://www.caddra.ca/wp-content/uploads/CADDRA-Guidelines-4th-Edition_-Feb2018.pdf |url-status=dead }}</ref><ref name="Bright2008">{{cite journal | vauthors = Bright GM | title = Abuse of medications employed for the treatment of ADHD: results from a large-scale community survey | journal = Medscape Journal of Medicine | volume = 10 | issue = 5 | pages = 111 | date = May 2008 | pmid = 18596945 | pmc = 2438483 }}</ref>
'''<big>By frequency</big>'''<ref name = TGA>{{cite web|title=Product Information DEXAMPHETAMINE TABLETS|work=TGA eBusiness Services|publisher=Aspen Pharma Pty Ltd|date=22 April 2009|accessdate=7 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00828-3|format=PDF}}</ref><ref name = DM>{{cite web|title=DEXTROAMPHETAMINE SULFATE tablet |work=DailyMed|publisher=Barr Laboratories Inc.|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ec2d13f3-d14f-47e4-abe9-7763f95a8e94|date=October 2013|accessdate=7 November 2013}}</ref><ref name = MS>{{cite web|title=dextroamphetamine (Rx) - Dexedrine, Liquadd, more...|accessdate=7 November 2013|url=http://reference.medscape.com/drug/dexedrine-liquadd-dextroamphetamine-342998|work=Medscape Reference|publisher=WebMD}}</ref><ref>{{cite journal |author=Vitiello B|title=Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function |journal=Child Adolesc Psychiatr Clin N Am |volume=17 |issue=2 |pages=459–74, xi|year=2008|pmid=18295156|pmc=2408826 |doi=10.1016/j.chc.2007.11.010}}</ref><ref></ref><ref>{{Cite journal|author=Vitiello B |title=Understanding the Risk of Using Medications for ADHD with Respect to Physical Growth and Cardiovascular Function |journal=Child Adolesc Psychiatr Clin N Am|volume=17 |issue=2 |pages=459–74, xi|year=2008|pmid=18295156|pmc=2408826|doi=10.1016/j.chc.2007.11.010}}</ref>


The reason for using crushed ]s for insufflation and injection ] is evidently due to the instant-release forms of the drug seen in tablet preparations often containing a sizable amount of inactive binders and fillers alongside the ] d-amphetamine, such as ].<ref name="Contextual conditioning">{{cite journal | vauthors = Childs E, de Wit H | title = Contextual conditioning enhances the psychostimulant and incentive properties of d-amphetamine in humans | journal = Addiction Biology | date = November 2013 | volume = 18 | issue = 6 | pages = 985–992 | pmid = 22129527 | pmc = 4242554 | doi = 10.1111/j.1369-1600.2011.00416.x }}</ref> Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.<ref name="NIDA ADHD stimulants" /> Chronic overuse of dextroamphetamine can lead to severe ], resulting in withdrawal symptoms when drug use stops.<ref name="NIDA ADHD stimulants" />
'''Very common (>10% frequency)'''
* Appetite loss
* Insomnia
* Abdominal pain


==Contraindications==
'''Common (1-10% frequency)'''
{{transcluded section|source=Amphetamine}}
{{colbegin|4}}
{{trim|{{#section-h:Amphetamine|Contraindications}}}}
* ]
* Palpitations
* Tremors
* Headache
* Dizziness
* Weight loss
* Dry mouth
* Diarrhea
* Fever
* Fatigue
* Infection
* Nausea/vomiting
* Dyspepsia (indigestion)
* Nervousness
* Emotional lability
{{colend}}

'''Unknown frequency adverse effects'''
* ]
* Sexual dysfunction
* Overstimulation
* Restlessness
* ]
* Tremor
* Exacerbation of motor and phonic tics and Tourette’s syndrome
* Hyperactivity

'''Serious adverse effects'''
{{colbegin|4}}
* Seizures
* Growth stunting
* Hypertension
* Stroke
* ] (heart attack)
* ] which can occur at therapeutic doses after chronic treatment.
* Mania/Hypomania
* Drug dependence
* ]
* Cardiomyopathy
{{colend}}

Recent studies by the FDA indicate that, in children, young adults, and adults, there is ''no association'' between serious adverse cardiovascular events (], ], and ]) and the use of dextroamphetamine or other ADHD stimulants in individuals with normal cardiovascular function.<ref>{{cite web|title=ADHD Medications and Risk of Stroke In Young and Middle-Aged Adults|url=http://www.fda.gov/downloads/Drugs/DrugSafety/UCM279877.pdf|accessdate=11 June 2013}}</ref><ref>{{cite web|title=ADHD Medications and Risk of Serious Coronary Heart Disease in Young and Middle-Aged Adults|url=http://www.effectivehealthcare.ahrq.gov/ehc/products/394/884/DEcIDE36_ADHDMeds-Adults_20111220.pdf|accessdate=11 June 2013}}</ref><ref>{{cite web|title=Attention Deficit Hyperactivity Disorder Medications and Risk of Serious Cardiovascular Disease in Children and Youth|url=http://www.effectivehealthcare.ahrq.gov/ehc/products/395/885/DEcIDE35_YouthADHD_20111031.pdf|accessdate=11 June 2013}}</ref>

==Overdosage==


==Adverse effects==
An overdose on amphetamine enantiomers is rarely fatal with appropriate care,<ref name="pmid23757186">{{cite journal | author = Spiller HA, Hays HL, Aleguas A | title = Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management | journal = CNS Drugs | volume = 27| issue = 7| pages = 531&ndash;543|date=June 2013 | pmid = 23757186 | doi = 10.1007/s40263-013-0084-8 }}</ref> but can lead to a number of different symptoms.<ref name="FDA Effects">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s024lbl.pdf | pages = 4&ndash;8 | work = United States Food and Drug Administration |date=June 2013 | accessdate = 7 October 2013}}</ref><ref name="FDA Abuse & OD" /> A moderate overdose may induce symptoms including: ], confusion, ], hypertension or hypotension, hyperthermia, ], ], severe agitation, ], ], ], and ].<ref name="FDA Effects" /><ref name="FDA Abuse & OD" /><ref name="Westfall" /> An extremely large overdose may produce symptoms such as ], amphetamine psychosis, ], ], ], ], ], ], ], rhabdomyolysis, ], and ].{{#tag:ref|<ref name="FDA Effects" /><ref name="FDA Abuse & OD" /><ref name="Westfall" /><ref name="Merck_Manual_Amphetamines">{{cite web | url = http://www.merckmanuals.com/professional/special_subjects/drug_use_and_dependence/amphetamines.html | author = O'Connor PG | title = Amphetamines | work = Merck Manual for Health Care Professionals | publisher = Merck |date=February 2012 | accessdate = 8 May 2012 }}</ref><ref name="Albertson_2011">{{cite book| editor = Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AHB | title = Poisoning & Drug Overdose | author = Albertson TE| year = 2011 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071668330 | chapter = Amphetamines | pages = 77&ndash;79 | edition = 6th }}</ref><ref name="Amph OD">{{cite web | title = Amphetamine Poisoning | url = http://emergency.unboundmedicine.com/emergency/ub/view/5-Minute_Emergency_Consult/307063/all/Amphetamine_Poisoning | work = Emergency Central | publisher = Unbound Medicine | date = 11 February 2011| accessdate = 11 June 2013 | author = Oskie SM, Rhee JW }}</ref><ref name="pmid17874986">{{cite journal | author = Isbister GK, Buckley NA, Whyte IM | title = Serotonin toxicity: a practical approach to diagnosis and treatment | journal = Med. J. Aust. | volume = 187 | issue = 6 | pages = 361&ndash;365 |date=September 2007 | pmid = 17874986 | doi = | url = https://www.mja.com.au/system/files/issues/187_06_170907/isb10375_fm.pdf }}</ref>| group = "ref-note" }} Fatal amphetamine poisoning usually also involves convulsions and ].<ref name="FDA Abuse & OD" /><ref name="Westfall" />
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Adverse effects}}}}


===Psychosis=== ==Overdose==
{{transcluded section|source=Amphetamine}}
{{Main|Stimulant psychosis}}
{{trim|{{#section-h:Amphetamine|Overdose}}}}
Abuse of amphetamines can result in a stimulant psychosis which may present with a variety of symptoms (e.g. ], ]s, ]s). A ] review on treatment for amphetamine, dextroamphetamine, and methamphetamine induced psychosis<ref name="Cochrane"/> states that about 5-15% of users fail to recover completely.<ref name="Hoffman">Hofmann FG. A handbook on drug and alcohol abuse: the biomedical aspects. 2nd Edition. New York: Oxford University Press, 1983.</ref> The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.<ref name="Cochrane">{{cite journal | author = Shoptaw SJ, Kao U, Ling W | title = Treatment for amphetamine psychosis (Review) | url = |journal = Cochrane Database of Systematic Reviews | year = 2009 | issue = 1 }}</ref> An ] may also develop occasionally as a treatment-emergent side effect.<ref name="Berman-2009">{{Cite journal | last1 = Berman | first1 = SM.| last2 = Kuczenski | first2 = R. | last3 = McCracken | first3 = JT. | last4 = London | first4 = ED. | title = Potential adverse effects of amphetamine treatment on brain and behavior: a review | journal = Mol Psychiatry | volume = 14 | issue = 2 | pages = 123–42 |date=Feb 2009 | doi = 10.1038/mp.2008.90 | pmid = 18698321 | pmc=2670101}}</ref><ref name="Berman-2009">{{Cite journal | last1 = Berman | first1 = SM. | last2 = Kuczenski |first2 = R. | last3 = McCracken | first3 = JT. | last4 = London | first4 = ED. | title = Potential adverse effects of amphetamine treatment on brain and behavior: a review |journal = Mol Psychiatry | volume = 14 | issue = 2 |pages = 123–42 |date=Feb 2009 | doi = 10.1038/mp.2008.90 | pmid = 18698321 | pmc = 2670101 }}</ref><ref>{{cite web|url=http://www.merck.com/mmpe/sec15/ch198/ch198k.htmlAmphetamines|publisher=Merck Sharpe and Dohme|accessdate=27 November 2013}}</ref>


===Withdrawal=== ==Interactions==
Many types of substances are known to ] with amphetamine, resulting in altered ] or ] of amphetamine, the interacting substance, or both.<ref name="FDA Pharmacokinetics" /><ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Inhibitors of the enzymes that metabolize amphetamine (e.g., ] and ]) will prolong its ], meaning that its effects will last longer.<ref name="FMO" /><ref name="Adderall FDA label">{{cite web | title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet | website=DailyMed | date=27 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 | access-date=28 March 2022}}</ref><ref name="Adderall XR FDA label">{{cite web | title=Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release | website=DailyMed | date=3 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0 | access-date=28 March 2022}}</ref> Amphetamine also interacts with {{abbr|MAOIs|monoamine oxidase inhibitors}}, particularly ] inhibitors, since both MAOIs and amphetamine increase ] catecholamines (i.e., norepinephrine and dopamine);<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> therefore, concurrent use of both is dangerous.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of ]s and ]s and increase the effects of ]s and ]s.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Amphetamine may also decrease the effects of ] and ]s due to its effects on blood pressure and dopamine respectively.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> ] may reduce the minimum ] of amphetamine when it is used for the treatment of ADHD.{{#tag:ref|The human ] contains a ] extracellular zinc ] which, upon zinc binding, inhibits dopamine ] and amplifies amphetamine-induced ] '']''.<ref name="Zinc binding sites + ADHD review">{{cite journal | vauthors = Krause J | title = SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder | journal = Expert Rev. Neurother. | volume = 8 | issue = 4 | pages = 611–625 | date = April 2008 | pmid = 18416663 | doi = 10.1586/14737175.8.4.611 | s2cid = 24589993 | quote = Zinc binds at&nbsp;... extracellular sites of the DAT , serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc on symptoms of ADHD . It should be stated that at this time with zinc is not integrated in any ADHD treatment algorithm.}}</ref><ref name="Review - cites 2002 amph-zinc primary study">{{cite journal | vauthors = Sulzer D | title = How addictive drugs disrupt presynaptic dopamine neurotransmission | journal = Neuron | volume = 69 | issue = 4 | pages = 628–649 | date = February 2011 | pmid = 21338876 | pmc = 3065181 | doi = 10.1016/j.neuron.2011.02.010 | quote = They did not confirm the predicted straightforward relationship between uptake and release, but rather that some compounds including AMPH were better releasers than substrates for uptake. Zinc, moreover, stimulates efflux of intracellular DA despite its concomitant inhibition of uptake (Scholze et al., 2002).}}</ref><ref name="Primary 2002 amph-zinc study">{{cite journal | vauthors = Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH | title = The role of zinc ions in reverse transport mediated by monoamine transporters | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 21505–21513 | date = June 2002 | pmid = 11940571 | doi = 10.1074/jbc.M112265200| doi-access = free}}</ref> The human ] and ] do not contain zinc binding sites.<ref name="Primary 2002 amph-zinc study" />|group="note"}}<ref name="Zinc and PEA">{{cite journal |vauthors=Scassellati C, Bonvicini C, Faraone SV, Gennarelli M | title = Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses | journal = J. Am. Acad. Child Adolesc. Psychiatry | volume = 51 | issue = 10 | pages = 1003–1019.e20 | date = October 2012 | pmid = 23021477 | doi = 10.1016/j.jaac.2012.08.015}}</ref>

While addiction is a serious risk with heavy recreational amphetamine use, it is unlikely to arise from typical medical use.<ref name="FDA Abuse & OD">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s024lbl.pdf | page = 11 | work = United States Food and Drug Administration |date=June 2013 | accessdate = 7 October 2013 }}</ref><ref name="Westfall" /><ref name="EncycOfPsychopharm">{{Cite book | author = Stolerman IP | editor = Stolerman IP | title = Encyclopedia of Psychopharmacology | year = 2010 | publisher = Springer | location = Berlin; London | isbn = 9783540686989 | page = 78 | quote = Although are also used as recreational drugs, with important neurotoxic consequences when abused, addiction is not a high risk when therapeutic doses are used as directed.}}</ref> ] is developed rapidly in amphetamine abuse; therefore, periods of extended use require increasing amounts of the drug in order to achieve the same effect.<ref>{{cite web
| title = Amphetamines: Drug Use and Abuse | work = Merck Manual Home Edition | publisher = Merck | url = http://www.merckmanuals.com/home/special_subjects/drug_use_and_abuse/amphetamines.html | accessdate = 28 February 2007 | archiveurl = http://web.archive.org/web/20070217053619/http://www.merck.com/mmhe/sec07/ch108/ch108g.html |date=February 2003 | archivedate = 17 February 2007}}</ref> According to a Cochrane Collaboration review on withdrawal in highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24&nbsp;hours of their last dose."<ref name="Cochrane Withdrawal">{{cite journal | author = Shoptaw SJ, Kao U, Heinzerling K, Ling W | title = Treatment for amphetamine withdrawal | journal = Cochrane Database Syst. Rev. | volume = | issue = 2 | pages = CD003021 | year = 2009 | pmid = 19370579 | doi = 10.1002/14651858.CD003021.pub2 | editor = Shoptaw SJ |quote = <br>The prevalence of this withdrawal syndrome is extremely common (Cantwell 1998; Gossop 1982) with 87.6% of 647 individuals with amphetamine dependence reporting six or more signs of amphetamine withdrawal listed in the DSM when the drug is not available (Schuckit 1999)...Withdrawal symptoms typically present within 24 hours of the last use of amphetamine, with a withdrawal syndrome involving two general phases that can last 3 weeks or more. The first phase of this syndrome is the initial “crash” that resolves within about a week (Gossop 1982;McGregor 2005)...}}</ref> This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for 3&ndash;4&nbsp;weeks with a marked "crash" phase occurring during the first week.<ref name="Cochrane Withdrawal" /> Amphetamine withdrawal symptoms can include ], ], ], ], ] or ], ] or ], anxiety, and ].<ref name="Cochrane Withdrawal" /> The review suggested that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms.<ref name="Cochrane Withdrawal" /> The {{abbr|USFDA|United States Food and Drug Administration}} does not indicate the presence of withdrawal symptoms following discontinuation of pharmaceutical amphetamine use after an extended period at therapeutic doses.<ref>{{cite web | title=Adderall IR Prescribing Information | url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011522s040lbl.pdf | work = United States Food and Drug Administration |date=March 2007 | accessdate = 4 November 2013 }}</ref><ref>{{cite web | title = Dexedrine Medication Guide | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/017078s046lbl.pdf | work = United States Food and Drug Administration |date=May 2013 | accessdate = 4 November 2013 }}</ref><ref>{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s024lbl.pdf | work = United States Food and Drug Administration |date=June 2013 | accessdate = 4 November 2013}}</ref>


==Pharmacology== ==Pharmacology==
{{Annotated image 4
|caption = Amphetamine enters the presynaptic neuron across the neuronal membrane or through {{abbr|DAT|dopamine transporter}}. Once inside, it binds to {{abbr|TAAR1|trace amine-associated receptor 1}} or enters synaptic vesicles through {{abbr|VMAT2|vesicular monoamine transporter 2}}. When amphetamine binds to TAAR1, it reduces dopamine receptor firing rate and triggers ] (PKA) and ] (PKC) signaling, resulting in DAT phosphorylation. Phosphorylated DAT then either operates in reverse or withdraws into the presynaptic neuron and ceases transport. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (yellow area).
|header = Pharmacodynamics of amphetamine enantiomers in a dopamine neuron
|header_align = center
|header_background = #F0F8FF
|alt = A pharmacodynamic model of amphetamine and TAAR1
|image = TAAR1 Dopamine.svg
|align = right
|image-width = 520
|image-left = 0
|image-top = 0
|width = 520
|height = 650
|annot-font-size = 13
|annot-text-align = center
|annotations =
{{Annotation|190|45|via ''']'''}}
}}


===Pharmacodynamics=== ===Pharmacodynamics===
{{Main section|Amphetamine|Pharmacodynamics}} {{hatnote|Main section: {{section link|Amphetamine|Pharmacodynamics}}}}
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|] of ] and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref
|-
| ] || 10.9 || 39.5 || >10,000 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012" /><ref name="Blough2008" />
|-
| Dextroamphetamine || 6.6–7.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| ] || 9.5 || 27.7 || {{abbr|ND|No data}} || <ref name="Forsyth2012">{{cite journal | vauthors = Forsyth AN | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>
|-
| ] || 12.3–13.8 || 8.5–24.5 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | year = 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref>
|-
| ] || 28.5 || 416 || 4,640 || <ref name="RothmanBaumannDersch2001" />
|-
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. See also ] for a larger table with more compounds. '''Refs:''' <ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}
{{Amphetamine pharmacodynamics}}
Amphetamine and its enantiomers have been identified as potent ]s of ] (TAAR1), a ], discovered in 2001, that is important for regulation of ] systems in the brain.<ref name="pmid11723224">{{cite journal | vauthors = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Molecular Pharmacology | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 | s2cid = 14140873 }}</ref><ref name="TAAR1 stereoselective" /> Activation of TAAR1 increases ] production via ] activation and inhibits the function of the ], ], and ], as well as inducing the release of these monoamine neurotransmitters (effluxion).<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–176 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="pmid11723224" /><ref name="pmid11459929">{{cite journal | vauthors = Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C | title = Trace amines: identification of a family of mammalian G protein-coupled receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 8966–8971 | date = July 2001 | pmid = 11459929 | pmc = 55357 | doi = 10.1073/pnas.151105198 | doi-access = free | bibcode = 2001PNAS...98.8966B }}</ref> Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called ].<ref name="E Weihe" /> When amphetamine is taken up by ], the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.<ref name="E Weihe">{{cite journal | vauthors = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | bibcode = 2011NYASA1216...86E }}</ref>


Dextroamphetamine (the ] ]) and ] (the ] enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.<ref name="TAAR1 stereoselective" /><ref name="WestfallDP">{{cite book |veditors=Brunton LL, Chabner BA, Knollmann BC | title = Goodman & Gilman's Pharmacological Basis of Therapeutics | year = 2010 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-162442-8 |vauthors=Westfall DP, Westfall TC | section = Miscellaneous Sympathomimetic Agonists | section-url = http://www.accessmedicine.com/content.aspx?aID=16661601 | edition = 12th }}</ref> Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.<ref name="TAAR1 stereoselective" /> Consequently, dextroamphetamine produces roughly three to four times more ] (CNS) stimulation than levoamphetamine;<ref name="TAAR1 stereoselective">{{cite journal |vauthors=Lewin AH, Miller GM, Gilmour B | title = Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | journal = Bioorg. Med. Chem. | volume = 19 | issue = 23 | pages = 7044–7048 | date = December 2011 | pmid = 22037049 | pmc = 3236098 | doi = 10.1016/j.bmc.2011.10.007 }}</ref><ref name="WestfallDP" /> however, levoamphetamine has slightly greater cardiovascular and peripheral effects.<ref name="WestfallDP" />
Amphetamine and its enantiomers have been identified as potent ]s of ] (aka "TAAR1"), a ], discovered in 2001, that is important for regulation of ] systems in the brain.<ref name="pmid11723224">{{cite journal | author = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Mol. Pharmacol. | volume = 60 | issue = 6 | pages = 1181–8 |date=December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181}}</ref><ref name="TAAR1 stereoselective" /> Activation of TAAR1 increases ] production via ] activation and inhibits the function of the ], ], and ], as well as induce effluxion of these neurotransmitters.<ref name="pmid11723224" /><ref name="pmid11459929">{{cite journal | author = Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C | title = Trace amines: identification of a family of mammalian G protein-coupled receptors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 16 | pages = 8966–71 |date=July 2001 | pmid = 11459929 | pmc = 55357 | doi = 10.1073/pnas.151105198 |bibcode = 2001PNAS...98.8966B }}</ref><ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–76 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref> Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called ].<ref name="E Weihe" /> When amphetamine is taken up by ], the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.<ref name="E Weihe">{{cite journal | author = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Ann. N. Y. Acad. Sci. | volume = 1216 | issue = | pages = 86–98 |date=January 2011 | pmid = 21272013 | doi = 10.1111/j.1749-6632.2010.05906.x }}</ref>

Dextroamphetamine (the ] ]) and ] (the ] enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.<ref name="Westfall">{{cite book | editor = Brunton LL, Chabner BA, Knollmann BC | title = Goodman & Gilman's Pharmacological Basis of Therapeutics | year = 2010 | publisher = McGraw-Hill | location = New York | isbn = 9780071624428 | author = Westfall DP, Westfall TC | section = Miscellaneous Sympathomimetic Agonists | sectionurl = http://www.accessmedicine.com/content.aspx?aID=16661601 | edition = 12th }}</ref><ref name="TAAR1 stereoselective" /> Dextroamphetamine is a more potent agonist of {{abbr|TAAR1|trace amine-associated receptor 1}} than levoamphetamine.<ref name="TAAR1 stereoselective" /> Consequently, dextroamphetamine produces roughly three to four times more {{abbr|CNS|central nervous system}} stimulation than levoamphetamine;<ref name="Westfall" /><ref name="TAAR1 stereoselective">{{cite journal | author= Lewin AH, Miller GM, Gilmour B | title=Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | journal=Bioorg. Med. Chem. |date=December 2011 | volume=19 | issue=23 | pages=7044&ndash;7048 | pmid=22037049 | doi= 10.1016/j.bmc.2011.10.007 | pmc= 3236098}}</ref> however, levoamphetamine has slightly greater cardiovascular and peripheral effects.<ref name="Westfall" />


===Related endogenous compounds=== ===Related endogenous compounds===
{{trim|{{#section-h:Amphetamine|Related endogenous compounds}}}}
{{More information|Trace amines}}
Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring molecules produced in the human body and brain.<ref name="Miller" /><ref name="Trace Amines" /> Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and {{nowrap|]}}, an ] of amphetamine (i.e., identical molecular formula).<ref name="Miller" /><ref name="Trace Amines" /> In humans, phenethylamine is produced in the body directly from ] by the same enzyme that converts ] into dopamine, ].<ref name="Trace Amines" /> In turn, {{nowrap|''N''‑methylphenethylamine}} is metabolized from phenethylamine by ], which the same enzyme that metabolizes norepinephrine into adrenaline.<ref name="Trace Amines">{{cite journal | author = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacol. Ther. | volume = 125 | issue = 3 | pages = 363&ndash;375 |date=March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005 | quote= '''Fig. 2.''' Synthetic and metabolic pathways for endogenous and exogenously administered trace amines and sympathomimetic amines...<br> Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2)...It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone...<br>Thus, MAO inhibitors potentiate the peripheral effects of indirectly acting sympathomimetic amines. It is not often realized, however, that this potentiation occurs irrespective of whether the amine is a substrate for MAO. An α-methyl group on the side chain, as in amphetamine and ephedrine, renders the amine immune to deamination so that they are not metabolized in the gut. Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut...<br> Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life,...}}</ref> Like amphetamine, both phenethylamine and {{nowrap|''N''‑methylphenethylamine}} regulate monoamine neurotransmission via {{abbr|TAAR1|trace amine-associated receptor 1}};<ref name="Miller" /> however, unlike amphetamine, both of these substances are broken down by ], and therefore have a shorter half-life than amphetamine.<ref name="Trace Amines" />


===Pharmacokinetics=== ===Pharmacokinetics===
{{transcluded section|source=Amphetamine}}

{{trim|{{#section-h:Amphetamine|Pharmacokinetics}}}}
Amphetamine is well absorbed from the gut, and ] is typically over 75% for dextroamphetamine.<ref name="Drugbank-dexamph">{{cite web | title=Dextroamphetamine | url=http://www.drugbank.ca/drugs/DB01576#pharmacology | work=DrugBank | publisher= University of Alberta | accessdate=5 November 2013 | date=8 February 2013 | section=Pharmacology }}</ref> However, oral availability varies with gastrointestinal pH.<ref name="FDA Interactions">{{cite web | title = Adderall XR Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021303s026lbl.pdf | pages = 8&ndash;10 | work = United States Food and Drug Administration |date=December 2013 | accessdate = 30 December 2013 }}</ref> Dextroamphetamine is a weak base with a ] of 9&ndash;10;<ref name="FDA Pharmacokinetics" /> consequently, when the pH is basic, more of the drug is in its ] soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut ].<ref name="FDA Pharmacokinetics" /><ref name="FDA Interactions" /> Conversely, an acidic pH means the drug is predominantly in its water soluble ]ic form, and less is absorbed.<ref name="FDA Pharmacokinetics" /><ref name="FDA Interactions" />

Approximately 15&ndash;40% of dextroamphetamine circulating in the bloodstream is bound to ]s.<ref name="Drugbank-amph">{{cite web | title=Amphetamine | url=http://www.drugbank.ca/drugs/DB00182#pharmacology | work=DrugBank | publisher= University of Alberta | accessdate=5 November 2013 | date=8 February 2013 | section=Pharmacology }}</ref>

The ] of dextroamphetamine varies with urine pH.<ref name="FDA Pharmacokinetics" /> At normal urine pH, the half-life of dextroamphetamine is 9&ndash;11&nbsp;hours.<ref name="FDA Pharmacokinetics" /> An acidic diet will reduce the half-life to 8&ndash;11 hours, while an alkaline diet will increase the range to 16&ndash;31 hours.<ref name="Pubchem Kinetics" /><ref>{{cite web| title=AMPHETAMINE| section=Biological Half-Life| url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+300-62-9| work=United States National Library of Medicine - Toxnet| publisher=Hazardous Substances Data Bank| accessdate=5 January 2014 |quote=Concentrations of (14)C-amphetamine declined less rapidly in the plasma of human subjects maintained on an alkaline diet (urinary pH > 7.5) than those on an acid diet (urinary pH < 6). Plasma half-lives of amphetamine ranged between 16-31 hr & 8-11 hr, respectively, & the excretion of (14)C in 24 hr urine was 45 & 70%.}}</ref> The immediate-release and extended release variants of dextroamphetamine salts reach peak plasma concentrations at 3&nbsp;hours and 7&nbsp;hours post-dose respectively.<ref name="FDA Pharmacokinetics" /> Dextromphetamine is eliminated via the kidneys, with 30&ndash;40% of the drug being excreted unchanged at normal urinary pH.<ref name="FDA Pharmacokinetics" /> When the urinary pH is basic, more of the drug is in its poorly water soluble free base form, and less is excreted.<ref name="FDA Pharmacokinetics" /> When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to as much as 75%, depending mostly upon whether urine is too basic or acidic, respectively.<ref name="FDA Pharmacokinetics" /> Amphetamine is usually eliminated within two days of the last oral dose.<ref name="Pubchem Kinetics" /> Apparent half-life and duration of effect increase with repeated use and accumulation of the drug.<ref name="Flomenbaum_2006">{{cite web | author = Richard RA | title = Chapter 5&mdash;Medical Aspects of Stimulant Use Disorders | series = Treatment Improvement Protocol 33 | year = 1999 | work = National Center for Biotechnology Information Bookshelf | publisher = Substance Abuse and Mental Health Services Administration | url = http://www.ncbi.nlm.nih.gov/books/NBK64323/ | section = Route of Administration}}</ref>

CYP2D6, ], and ] are the only enzymes currently known to metabolize amphetamine in humans.<ref name="DBH ref" /><ref name="FDA Pharmacokinetics" /><ref name="FMO" /><ref name="DrugBank Enzymes">{{cite web | title=Amphetamine | url=http://www.drugbank.ca/drugs/DB00182#enzymes | work=DrugBank | publisher= University of Alberta | accessdate=30 September 2013 | date=8 February 2013 | section=Enzymes }}</ref> Amphetamine has a variety of excreted metabolic products, including {{nowrap|]}}, {{nowrap|]}}, {{nowrap|]}}, ], ], ], and ].<ref name="FDA Pharmacokinetics" /><ref name="Pubchem Kinetics">{{cite web | title=Amphetamine | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007#x332 | work=Pubchem Compound | publisher = National Center for Biotechnology Information | accessdate=12 October 2013 | section=Biomedical Effects and Toxicity }}</ref><ref name="Metabolites">{{cite journal | author = Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G | title = Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection | journal = J. Pharm. Biomed. Anal. | volume = 30 | issue = 2 | pages = 247&ndash;255 |date=September 2002 | pmid = 12191709 | doi =10.1016/S0731-7085(02)00330-8 }}</ref> Among these metabolites, the active ] are {{nowrap|4‑hydroxyamphetamine}},<ref>{{cite web | title=p-Hydroxyamphetamine | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3651 | work=PubChem Compound | publisher = National Center for Biotechnology Information | accessdate=15 October 2013 | section=Compound Summary }}</ref> {{nowrap|4‑hydroxynorephedrine}},<ref>{{cite web | title=p-Hydroxynorephedrine | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11099 | work=PubChem Compound | publisher = National Center for Biotechnology Information | accessdate=15 October 2013 | section=Compound Summary }}</ref> and norephedrine.<ref>{{cite web | title=Phenylpropanolamine | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=26934 | work=PubChem Compound | publisher = National Center for Biotechnology Information | accessdate=15 October 2013 | section=Compound Summary }}</ref>

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.<ref name="FDA Pharmacokinetics" /><ref name="Pubchem Kinetics" /> The known pathways include:<ref name="FDA Pharmacokinetics" /><ref name="FMO" /><ref name="Metabolites" />
{{Amphetamine Pharmacokinetics|caption=The primary active metabolites of amphetamine are {{nowrap|4-hydroxyamphetamine}} and norephedrine;<ref name="Metabolites" /> however, most of an administered dose is excreted as amphetamine itself and the inactive metabolites.<ref name="FDA Pharmacokinetics" />}}
{{clear}} {{clear}}


==History, society, and culture== ==History, society, and culture==
{{Main|History and culture of amphetamines}} {{Main|History and culture of amphetamines}}
] amphetamine was first ] under the chemical name "phenylisopropylamine" in ], 1887 by the Romanian chemist ].<ref></ref> It was not widely marketed until 1932, when the pharmaceutical company ] (now known as ]) introduced it in the form of the ] inhaler for use as a ]. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base,<ref group="n">Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.</ref> not a chloride or sulfate salt. ] amphetamine was first ] under the chemical name "phenylisopropylamine" in ], 1887 by the Romanian chemist ]. It was not widely marketed until 1932, when the pharmaceutical company ] (now known as ]) introduced it in the form of the ] inhaler for use as a ]. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base,<ref group="note">Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.</ref> not a chloride or sulfate salt.


Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dexamfetamine, and in 1937 Smith, Kline, and French introduced tablets under the tradename Dexedrine.<ref>{{cite web|title=Dexedrine|url=http://www.medic8.com/medicines/Dexedrine.html|work=Medic8|accessdate=27 November 2013}}</ref> In the United States, Dexedrine was approved to treat ], ], depression, and obesity. In Canada, epilepsy and parkinsonism were also approved indications.<ref></ref> Dexamfetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dexamfetamine and ] (a ]) sold under the tradename ] and, in the 1950s, an extended release capsule (the "Spansule").<ref></ref> Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically the dextroamphetamine isomer, and in 1937 Smith, Kline, and French introduced tablets under the brand name '''Dexedrine'''.<ref>{{cite web|title=Dexedrine|url=http://www.medic8.com/medicines/Dexedrine.html|website=Medic8|access-date=27 November 2013|url-status=dead|archive-url=https://web.archive.org/web/20091219120223/http://www.medic8.com/medicines/Dexedrine.html|archive-date=19 December 2009}}</ref> In the United States, Dexedrine was approved to treat ] and ] (ADHD).<ref name="Dexedrine FDA label" /> In Canada ]s once included epilepsy and parkinsonism.<ref>{{cite web| url =http://www.mentalhealth.com/drug/p30-d04.html| title =Dextroamphetamine | website =Internet Mental Health| archive-url =https://web.archive.org/web/20060427084347/http://www.mentalhealth.com/drug/p30-d04.html| access-date =6 September 2015| archive-date=27 April 2006}}</ref> Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and ] (a ]) sold under the brand name ] and, in the 1950s, an extended release capsule (the "Spansule").<ref>{{cite web|url=http://www.weitzlux.com/Dexedrine/information_403484.html |title=Information on Dexedrine: A Quick Review {{pipe}} Weitz & Luxenberg |publisher=Weitzlux.com |date=31 August 2013 |access-date=5 January 2017}}</ref> Preparations containing dextroamphetamine were also used in ] as a treatment against ].<ref name="Amph Uses">{{cite journal |vauthors=Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present—a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–96 | date = June 2013 | pmid = 23539642 | doi = 10.1177/0269881113482532 | pmc = 3666194 }}</ref>


It quickly became apparent that dexamfetamine and other amphetamines had a high potential for ], although they were not heavily ] until 1970, when the ] was passed by the United States Congress. Dexamfetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use.<ref></ref> Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain).<ref name="pharaman"> (2nd edition), Marshall Sittig, Volume 1, Noyes Publications ISBN 978-0-8155-1144-1</ref> It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for ], although they were not heavily ] until 1970, when the ] was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use.<ref>{{cite web | vauthors = King DG | date = 4 January 2017 | url = http://www.denton.handwritingexperts.com/articles/prescriptionforgery1.html | title = Prescription Forgery | work = Handwriting Services International | archive-url = https://web.archive.org/web/20080705185842/http://www.denton.handwritingexperts.com/articles/prescriptionforgery1.html | archive-date = 5 July 2008 }}</ref> Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain).<ref name="pharaman">{{cite book | url = http://www.knovel.com/web/portal/browse/display?_EXT_KNOVEL_DISPLAY_bookid=598 | title = Pharmaceutical Manufacturing Encyclopedia | date = January 1988 | edition = 2nd | veditors = Sittig M | volume = 1 | publisher = Noyes Publications | isbn = 978-0-8155-1144-1}}</ref> It became popular on the ] scene in England in the early 1960s, and carried through to the ] scene in the north of England to the end of the 1970s.


In October 2010, ] sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).<ref>{{cite web|title=Dexedrine FAQs|url=http://www.dexedrine.net/faq.asp}}</ref> In October 2010, ] sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).<ref>{{cite web|title=Dexedrine FAQs|url=http://www.dexedrine.net/faq.asp|url-status=dead|archive-url=https://web.archive.org/web/20110617013326/http://www.dexedrine.net/faq.asp|archive-date=17 June 2011}}</ref>


The U.S. Air Force uses dexamfetamine as one of its "go pills", given to pilots on long missions to help them remain focused and alert. Conversely, "no-go pills" are used after the mission is completed, to combat the affects of the mission and "go-pills".<ref>http://www.nbcnews.com/id/3071789/ns/us_news-only/t/go-pills-war-drugs/</ref><ref name=airforcegopills></ref><ref>{{Cite journal|pmid=7661838|year=1995|last1=Emonson|first1=DL|last2=Vanderbeek|first2=RD|title=The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm|volume=66|issue=3|pages=260–3|journal=Aviation, space, and environmental medicine}}</ref><ref>, msnbc, 9 January 2003</ref> The ] was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer ] medications or awakeness promoting agents with different side effect profiles, such as ], are being investigated and sometimes issued for this reason.<ref name=airforcegopills /> The U.S. Air Force uses dextroamphetamine as one of its "go pills", given to pilots on long missions to help them remain focused and alert. Conversely, "no-go pills" are used after the mission is completed, to combat the effects of the mission and "go-pills".<ref name="Bonné_2003">{{cite web | vauthors = Bonné J |url=https://www.nbcnews.com/id/wbna3071789 |title='Go pills': A war on drugs? |work=NBC News |date=9 January 2003 |access-date=5 January 2017}}</ref><ref name=airforcegopills>{{cite web | vauthors = Woodring JC |url=http://www.af.mil/news/story.asp?id=123007615 |title=Air Force scientists battle aviator fatigue |access-date=5 January 2017 |url-status= dead |archive-url=https://web.archive.org/web/20121014113247/http://www.af.mil/news/story.asp?id=123007615 |archive-date=14 October 2012 }}</ref><ref>{{cite journal |vauthors=Emonson DL, Vanderbeek RD | title = The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm | journal = Aviation, Space, and Environmental Medicine | volume = 66 | issue = 3 | pages = 260–3 | year = 1995 | pmid = 7661838 }}</ref> The ] was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer ] medications or awakeness promoting agents with different side effect profiles, such as ], are being investigated and sometimes issued for this reason.<ref name=airforcegopills />


===Formulations=== ===Formulations===

]
{| class="wikitable sortable" style="text-align:center" style="text-align:center; width:430px;" {| class="wikitable sortable" style="text-align:center;"
|+ Dextroamphetamine pharmaceuticals and prodrugs{{#tag:ref|These represent the current brands in the United States, except Dexedrine instant release tablets. Dexedrine tablets, introduced in 1937, is discontinued but available as Zenzedi and generically;<ref name="Amph Uses" /><ref>{{cite web | title=Drugs@FDA: Dexedrine | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process | access-date=28 March 2022}}</ref> Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976.<ref>{{cite web | title=Drugs@FDA: Dexedrine | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=017078 | access-date=28 March 2022}}</ref><ref>{{cite web|title = Drugs@FDA: Dexedrine: Label and Approval History|url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=017078&DrugName=DEXEDRINE&ActiveIngred=DEXTROAMPHETAMINE%2520SULFATE&SponsorApplicant=AMEDRA%2520PHARMS&ProductMktStatus=1&goto=Search.Label_ApprovalHistory|website = U.S. ] (FDA)|access-date = 30 December 2015|quote = 08/02/1976 ... Approval|archive-date = 28 August 2021|archive-url = https://web.archive.org/web/20210828060742/https://www.accessdata.fda.gov/scripts/cder/daf/|url-status = dead}}</ref> Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935<ref>{{cite journal | vauthors = Strohl MP | title = Bradley's Benzedrine studies on children with behavioral disorders | journal = The Yale Journal of Biology and Medicine | volume = 84 | issue = 1 | pages = 27–33 | date = March 2011 | pmid = 21451781 | pmc = 3064242 | quote = Bradley experimented with Benzedrine sulfate, a drug marketed to doctors by the company Smith, Kline & French (SKF) between 1935 and 1937... }}</ref><ref name="Amph Uses" /> and discontinued sometime after 1982.<ref name="Amph Uses" /><ref>{{cite web|url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist|title = FDA Approved Drug Products: Label and Approval History (Benzedrine)|website = U.S. ] (FDA)|access-date = 11 March 2016|quote = Action Date 5/11/1982, Supplement Number 007, Approval Type Chemistry}}</ref>| group = "note" }}
! scope="col" | Brand<br />name ! scope="col" | Brand<br />name
! scope="col" | ] ! scope="col" | ]
! scope="col" class="unsortable" style="text-align:center"| ]<br />of salts ! scope="col" class="unsortable" style="text-align:center" | ]
! scope="col"| Dosage<br />form ! scope="col"| Dosage<br />form
! scope="col" class="unsortable" | <small>Source</small> ! scope="col" class="unsortable" | Marketing<br />start&nbsp;date
! scope="col" class="unsortable" | <small>Sources</small>
|- |-
| Adderall || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small><!-- DO NOT CHANGE THIS RATIO: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194/table/table1-0269881113482532/ -->|| tablet || 1996 || <ref name="Amph Uses" /><ref name="NDCD" />
| Adderall || – || 3:1 || tablet || <ref name="NDCD" /><ref name="DrugBank1">{{cite web | title=Amphetamine | url=http://www.drugbank.ca/drugs/DB00182#identification | section=Description, Synonyms, Brand names, and Brand mixtures | work=DrugBank | publisher= University of Alberta | accessdate=13 October 2013 | date=8 February 2013 }}</ref>
|- |-
| Adderall&nbsp;XR || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small> || capsule || 2001 || <ref name="Amph Uses" /><ref name="NDCD">{{cite web | title = National Drug Code Amphetamine Search Results | url = http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | website = National Drug Code Directory|publisher=U.S. ] (FDA) | access-date = 16 December 2013 | archive-url = https://web.archive.org/web/20131216080856/http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | archive-date=16 December 2013}}</ref>
| Adderall XR || – || 3:1 || capsule || <ref name="NDCD" /><ref name="DrugBank1" />
|- |-
| Mydayis || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small> || capsule || 2017 || <ref name="Mydayis">{{cite web | title=Mydayis- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate capsule, extended release | website=DailyMed | date=28 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=141a7970-3f06-44ea-9ab7-aeece2c085fc | access-date=21 January 2023}}</ref>
| Dexedrine || dextroamphetamine sulfate || 1:0 || capsule || <ref name="NDCD" />
|- |-
| Adzenys XR-ODT || amphetamine || 3:1&nbsp;<small>(base)</small> || ] || 2016 || <ref name="Adzenys">{{cite web | title=Adzenys XR-ODT- amphetamine tablet, orally disintegrating | website=DailyMed | date=10 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c1179269-00b5-48ea-972d-31e614e99b7e | access-date=21 January 2023}}</ref><ref name="FDA Adzenys approval date">{{cite web | title=Drug Approval Package: Adzenys XR-ODT (amphetamine) | website=U.S. ] (FDA) | date=27 January 2016 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/204326Orig1_toc.cfm | access-date=21 January 2023}}</ref>
| ProCentra || dextroamphetamine sulfate || 1:0 || tablet || <ref name="NDCD" />
|- |-
| Dyanavel&nbsp;XR || amphetamine ||3.2:1&nbsp;<small>(base)</small> ||suspension || 2015 || <ref name="Dyanavel" /><ref name="FDA Dyanavel approval date">{{cite web | title=Drug Approval Package: Dyanavel XR | website=U.S. ] (FDA) | date=21 March 2022 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/210526Orig1s000TOC.cfm | access-date=21 January 2023}}</ref>
| Vyvanse || lisdexamfetamine dimesylate || 1:0|| capsule || <ref name="Vyvanse">{{cite web | title=Lisdexamfetamine | url=http://www.drugbank.ca/drugs/DB01255#identification | work=Drugbank | publisher= University of Alberta | accessdate=13 October 2013 | date=8 February 2013 | section=Identification }}</ref>
|- |-
| Evekeo || amphetamine sulfate || 1:1&nbsp;<small>(salts)</small> || tablet || 2012 || <ref name="Evekeo"/><!-- defined by transclusion from Amphetamine|Contraindications --> <ref name="Racemic amph - FDA Evekeo status">{{cite web | title=Evekeo | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=200166 | website=U.S. ] (FDA) | access-date=11 August 2015}}</ref>
| Zenzedi || dextroamphetamine sulfate || 1:0 || liquid || <ref name="NDCD">{{cite web | title = National Drug Code Amphetamine Search Results | url = http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | work = National Drug Code Directory|publisher=United States Food and Drug Administration | accessdate = 16 December 2013 | archiveurl = http://web.archive.org/web/20131216080856/http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | archivedate = 7 February 2014}}</ref>
|-
| Dexedrine || ''' dextroamphetamine&nbsp;sulfate''' || 1:0&nbsp;<small>(salts)</small> || capsule || 1976 || <ref name="Amph Uses" /><ref name="NDCD" />
|-
| Zenzedi || '''dextroamphetamine&nbsp;sulfate''' || 1:0&nbsp;<small>(salts)</small> || tablet || 2013 || <ref name="NDCD" />
|-
| rowspan=2 | Vyvanse || rowspan=2 | lisdexamfetamine&nbsp;dimesylate || rowspan=2 | 1:0&nbsp;<small>(prodrug)</small> || capsule || rowspan=2 | 2007 || rowspan=2 | <ref name="Amph Uses" /><ref name=USVyvanselabel />
|-
| tablet
|-
| Xelstrym || '''dextroamphetamine''' || 1:0&nbsp;<small>(base)</small> || patch || 2022 || <ref name="Xelstrym FDA label" />
|} |}

==== Transdermal Dextroamphetamine Patches ====
Dextroamphetamine is available as a ] containing dextroamphetamine base under the brand name Xelstrym.<ref name="Xelstrym FDA label" />


==== Dextroamphetamine sulfate ==== ==== Dextroamphetamine sulfate ====
In the United States, ] (IR) formulations of dextroamphetamine ] are available generically as 5&nbsp;mg and 10&nbsp;mg tablets, marketed by Barr (]), ], Wilshire Pharmaceuticals, ] and CorePharma. Previous IR tablets sold under the brand names Dexedrine and Dextrostat have been discontinued but in 2015, IR tablets became available by the brand name Zenzedi, offered as 2.5&nbsp;mg, 5&nbsp;mg, 7.5&nbsp;mg, 10&nbsp;mg, 15&nbsp;mg, 20&nbsp;mg and 30&nbsp;mg tablets.<ref>{{cite web|url=http://zenzedi.com/ |title=Zenzedi (dextroamphetamine sulfate, USP) |publisher=Zenzedi.com |access-date=5 January 2017}}</ref> Dextroamphetamine sulfate is also available as a ] (CR) capsule preparation in strengths of 5&nbsp;mg, 10&nbsp;mg, and 15&nbsp;mg under the brand name Dexedrine Spansule, with generic versions marketed by Barr and Mallinckrodt. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5&nbsp;mg dextroamphetamine.<ref>{{cite web | url = http://www.fsclabs.com/ProCentra.html | title = ProCentra (dextroamphetamine sulfate 5 mg/5 mL Oral Solution) | work = FSC Laboratories | archive-url = https://web.archive.org/web/20101005052859/http://www.fsclabs.com/ProCentra.html | archive-date = 5 October 2010 }}</ref> The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.<ref>{{cite patent | inventor = Mickle T, Krishnan S, Bishop B, Lauderback C, Moncrief JS, Oberlender R, Piccariello T, Paul BJ, Verbicky CD | gdate = 2010 | title = Abuse-resistant amphetamine prodrugs | country = US | number = 7655630 | assign1 = Takeda Pharmaceutical Co Ltd }}</ref>
]


In Australia, dexamfetamine is available in bottles of 100 instant release 5&nbsp;mg tablets as a ]<ref>{{cite journal|doi=10.18773/austprescr.1995.064 |title=Stimulant treatment for attention deficit hyperactivity disorder |journal=Australian Prescriber |volume=18 |issue=3 |pages=60–63 |year=1995 | vauthors = Hazell P |doi-access= }}</ref> or slow release dextroamphetamine preparations may be compounded by individual chemists.<ref>{{cite web |url=http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp |title=Pharmaceutical Services |publisher=.health.nsw.gov.au |access-date=5 January 2017 |url-status=dead |archive-url=https://web.archive.org/web/20130505045845/http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp |archive-date=5 May 2013 }}</ref> In the United Kingdom, it is available in 5&nbsp;mg instant release sulfate tablets under the generic name dexamfetamine sulfate as well as 10&nbsp;mg and 20&nbsp;mg strength tablets under the brand name Amfexa. It is also available in generic dexamfetamine sulfate 5&nbsp;mg/ml oral sugar-free syrup.<ref>{{cite web |title=Dexamfetamine sulphate - Medicinal forms |url=https://bnf.nice.org.uk/medicinal-forms/dexamfetamine-sulfate.html |website=British National Formulary |publisher=BMJ Group and Pharmaceutical Press (Royal Pharmaceutical Society) |access-date=9 November 2019}}</ref> The brand name Dexedrine was available in the United Kingdom prior to ] disinvesting <!-- selling license to? --> the product to another pharmaceutical company (]).<ref>{{cite journal | title = Dexamfetamine – Prescribe Generically | url = http://www.ipnsm.hscni.net/news/RedAmberNewsNov10.pdf | journal = Red/Amber News | issue = 22 | archive-url = https://web.archive.org/web/20130518094535/http://www.ipnsm.hscni.net/news/RedAmberNewsNov10.pdf | archive-date=18 May 2013 | page = 2 | publisher = Interface Pharmacist Network Specialist Medicines (IPNSM) | date = November 2010 | access-date = 20 April 2012 }}</ref>
In the United States, an ] (IR) tablet preparation of the salt dexamfetamine ] is approved under the brand names Dexedrine and Dextrostat, in 5&nbsp;mg and 10&nbsp;mg strengths,{{citation needed|date=April 2013}} and generic formulations from ] and recently Wilshire Pharmaceuticals. It is also available as a capsule preparation of ] (CR) dexamfetamine sulfate, under the brand names Dexedrine SR and Dexedrine Spansule, in the strengths of 5&nbsp;mg, 10&nbsp;mg, and 15&nbsp;mg. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5&nbsp;mg dexamfetamine.<ref></ref>

In Australia, dexamfetamine is available in bottles of 100 instant release 5&nbsp;mg tablets as a ].<ref></ref> or slow release dexamfetamine preparations may be compounded by individual chemists.<ref>http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp</ref> Similarly, in the United Kingdom it is only available in 5&nbsp;mg instant release sulfate tablets under the generic name dexamfetamine sulphate having had been available under the brand name Dexedrine prior to ] disinvesting <!-- selling license to?--> the product to another pharmaceutical company (]).<ref>"", p2. Interface Pharmacist Network Specialist Medicines (IPNSM). www.ipnsm.hscni.net. Retrieved 20 April 2012.</ref>


==== Lisdexamfetamine ==== ==== Lisdexamfetamine ====
{{Main|Lisdexamfetamine}} {{Main|Lisdexamfetamine}}
Dextroamphetamine is the active ] of the ] lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name ] (lisdexamfetamine di]). Dextroamphetamine is liberated from lisdexamfetamine enzymatically following contact with red blood cells. The conversion is rate-limited by the enzyme, which prevents high blood concentrations of dextroamphetamine and reduces lisdexamfetamine's drug liking and ] at clinical doses.<ref>{{cite journal | vauthors = Hutson PH, Pennick M, Secker R | title = Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug | journal = Neuropharmacology | volume = 87 | pages = 41–50 | date = December 2014 | pmid = 24594478 | doi = 10.1016/j.neuropharm.2014.02.014 | s2cid = 37893582 }}</ref><ref>{{cite web | vauthors = Elayan I | url = https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf | title = NRP-104 (lisdexamphetamine dimesylate) | work = Pharmacology/Toxicology Review and Evaluation | publisher = U.S. Food and Drug Administration | date = 2006 | pages = 18–19 }}</ref> Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as ], and chewable tablets, and in seven strengths; 10&nbsp;mg, 20&nbsp;mg, 30&nbsp;mg, 40&nbsp;mg, 50&nbsp;mg, 60&nbsp;mg, and 70&nbsp;mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.<ref>{{cite journal | vauthors = Mohammadi M, Akhondzadeh S | title = Advances and considerations in attention-deficit/hyperactivity disorder pharmacotherapy | journal = Acta Medica Iranica | volume = 49 | issue = 8 | pages = 487–498 | date = September 2011 | pmid = 22009816 | url = http://acta.tums.ac.ir/index.php/acta/article/view/4380 | access-date = 12 March 2014 }}</ref><ref>{{cite journal | vauthors = Heal DJ, Buckley NW, Gosden J, Slater N, France CP, Hackett D | title = A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil | journal = Neuropharmacology | volume = 73 | pages = 348–358 | date = October 2013 | pmid = 23748096 | doi = 10.1016/j.neuropharm.2013.05.021 | s2cid = 25343254 }}</ref><ref>{{cite journal | vauthors = Rowley HL, Kulkarni R, Gosden J, Brammer R, Hackett D, Heal DJ | title = Lisdexamfetamine and immediate release d-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity | journal = Neuropharmacology | volume = 63 | issue = 6 | pages = 1064–1074 | date = November 2012 | pmid = 22796358 | doi = 10.1016/j.neuropharm.2012.07.008 | s2cid = 29702399 }}</ref>
Dexamfetamine is the active ] of the ] lisdexamfetamine (L-lysine-d-amphetamine), available by the brand name ]. Lisdexamfetamine is metabolised in the gastrointestinal tract, while dextroamphetamine's metabolism is ].<ref></ref> Lisdexamfetamine is therefore an inactive compound until it is converted into an active compound by the ]. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dexamfetamine into the body. Vyvanse is available as ], and in six strengths; 20&nbsp;mg, 30&nbsp;mg, 40&nbsp;mg, 50&nbsp;mg, 60&nbsp;mg, and 70&nbsp;mg. The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948,<ref>Moore, Elaine.. McFarland, 2010, p. 91.</ref> thus a 30&nbsp;mg-strength Vyvanse capsule is molecularly equivalent to 8.844&nbsp;mg dexamfetamine base.


==== Adderall ==== ====Adderall====
]
{{main|Adderall}} {{main|Adderall}}
]
Another pharmaceutical that contains dextroamphetamine is Adderall. The drug formulation of Adderall (both controlled and instant release forms) is:
Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> It is available as immediate release (IR) tablets and extended release (XR) capsules.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Adderall contains equal amounts of four amphetamine salts:<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" />
* One-quarter racemic (d,l-)amphetamine ] ]
* One-quarter dextroamphetamine ]
* One-quarter dextroamphetamine ]
* One-quarter racemic (d,l-)amphetamine sulfate

Adderall has a total amphetamine base equivalence of 63%.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> While the enantiomer ratio by dextroamphetamine salts to levoamphetamine salts is 3:1,<!-- REF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194/table/table1-0269881113482532/ --> the amphetamine base content is 75.9% dextroamphetamine, 24.1% levoamphetamine. {{#tag:ref|Calculated by dextroamphetamine base percent / total amphetamine base percent = 47.49/62.57 = 75.90% from table: Amphetamine base in marketed amphetamine medications. The remainder is levoamphetamine.| group = "note" }}

{{Amphetamine base in marketed amphetamine medications}}


== Research ==
::One-quarter racemic (d,l-)amphetamine ] ]
::One-quarter dextroamphetamine ]
::One-quarter dextroamphetamine sulfate
::One-quarter racemic (d,l-)amphetamine sulfate


=== Schizophrenia ===
Adderall is roughly three-quarters dextroamphetamine, with it accounting for 72.7% of the amphetamine base in Adderall (the remaining percentage is ]).
Dextroamphetamine reduces the ] of ], and has been shown to enhance the effects of auditory discrimination training in schizophrenic patients.<ref>{{cite journal |vauthors=Lindenmayer JP, Nasrallah H, Pucci M, James S, Citrome L |date=July 2013 |title=A systematic review of psychostimulant treatment of negative symptoms of schizophrenia: challenges and therapeutic opportunities |journal=Schizophrenia Research |volume=147 |issue=2-3 |pages=241–252 |doi=10.1016/j.schres.2013.03.019 |pmid=23619055}}</ref><ref>{{cite journal |vauthors=van Kammen DP, Boronow JJ |date=April 1988 |title=Dextro-amphetamine diminishes negative symptoms in schizophrenia |journal=International Clinical Psychopharmacology |volume=3 |issue=2 |pages=111–121 |doi=10.1097/00004850-198804000-00002 |pmid=3294284}}</ref><ref>{{cite journal |display-authors=6 |vauthors=Swerdlow NR, Tarasenko M, Bhakta SG, Talledo J, Alvarez AI, Hughes EL, Rana B, Vinogradov S, Light GA |date=July 2017 |title=Amphetamine Enhances Gains in Auditory Discrimination Training in Adult Schizophrenia Patients |journal=Schizophrenia Bulletin |volume=43 |issue=4 |pages=872–880 |doi=10.1093/schbul/sbw148 |pmc=5472129 |pmid=27798224}}</ref>{{clear}}


==Notes== ==Notes==
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==Reference notes==
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==References== ==References==
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==External links== ==External links==
{{Commons category}}
*
* {{cite book | url = http://www.inchem.org/documents/pims/pharm/pim178.htm | title = Poison Information Monograph | chapter = PIM 178: Dexamphetamine Sulphate) | publisher = International Programme on Chemical Safety (IPCS) Chemical Safety Information from Intergovernmental organizations (INCHEM) }}
*
* (PIM 178: Dexamphetamine Sulphate)


{{Amphetamine|state=expanded}} {{Amphetamine|state=expanded}}
{{ADHD pharmacotherapies}}
{{Monoamine releasing agents}}
{{Monoaminergic activity enhancers}}
{{TAAR ligands}}
{{Phenethylamines}} {{Phenethylamines}}
{{Stimulants}}
{{Psychostimulants, agents used for ADHD and nootropics}}
{{Dopaminergics}}
{{GlaxoSmithKline}} {{GlaxoSmithKline}}
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