Misplaced Pages

Amantadine: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively
Page 1
Page 2
← Previous editContent deleted Content addedVisualWikitext
Revision as of 14:28, 21 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit Latest revision as of 20:15, 5 January 2025 edit undo47.184.137.10 (talk) copyedit 
(486 intermediate revisions by more than 100 users not shown)
Line 1: Line 1:
{{Short description|Medication used to treat dyskinesia}}
{{Distinguish|Adamantine (disambiguation){{!}}Adamantine|Adamantane|Amanitin (disambiguation){{!}}Amanitin}}
{{Use American English|date=July 2019}}
{{Use dmy dates|date=February 2022}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox {{Drugbox
| Watchedfields = changed | Watchedfields = changed
| verifiedrevid = 443382074 | verifiedrevid = 456683223
| image = Amantadine.svg
| IUPAC_name = adamantan-1-amine
| width = 115px
| image = Amantadine stereo.png
| width = 150 | alt =
| image2 = Adamantadine-3D-balls.png | image2 = Amantadine ball-and-stick model.png
| width2 = 150px
| alt2 =
| caption =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Symmetrel | pronounce =
| tradename = Gocovri, Symadine, Symmetrel, others
| Drugs.com = {{drugs.com|monograph|amantadine-hydrochloride}} | Drugs.com = {{drugs.com|monograph|amantadine-hydrochloride}}
| MedlinePlus = a682064 | MedlinePlus = a682064
| DailyMedID = Amantadine
| pregnancy_category = C
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="TGA"/>
| pregnancy_category=
| routes_of_administration = ]
| class =
| ATC_prefix = N04
| ATC_suffix = BB01
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="TGA" />
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |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=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_CA_comment =
| legal_status = ]: ]
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Trilasym 50 mg/ 5 ml Oral Solution – Summary of Product Characteristics (SmPC) | website=(emc) | date=24 September 2019 | url=https://www.medicines.org.uk/emc/product/10262/smpc | access-date=26 March 2020 | archive-date=26 March 2020 | archive-url=https://web.archive.org/web/20200326213007/https://www.medicines.org.uk/emc/product/10262/smpc | url-status=dead }}</ref>
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Gocovri FDA label" /><ref name="Gocovri FDA label2" />
| routes_of_administration = oral
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = 86–90%<ref name="TGA">{{cite web|title=Symmetrel (amantadine hydrochloride)|work=TGA eBusiness Services|publisher=Novartis Pharmaceuticals Australia Pty Limited|date=29 June 2011|access-date=24 February 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04197-3|format=PDF}}</ref>
| bioavailability = well absorbed
| protein_bound = approx 67% | protein_bound = 67%<ref name="TGA"/>
| metabolism = negligible | metabolism = Minimal (mostly to acetyl metabolites)<ref name="TGA"/>
| metabolites =
| elimination_half-life = 10-14 hours, in renal impairment up to 7-10 days
| excretion = ] | onset =
| elimination_half-life = 10–31 hours<ref name="TGA"/>
| duration_of_action =
| excretion = Urine<ref name="TGA"/>


<!--Identifiers--> <!-- Identifiers -->
| index2_label = as HCl
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 768-94-5 | CAS_number = 768-94-5
| ATC_prefix = N04 | CAS_number2 = 665-66-7
| CAS_supplemental =
| ATC_suffix = BB01
| PubChem = 2130 | PubChem = 2130
| PubChem2 = 64150
| IUPHAR_ligand = 4128
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00915 | DrugBank = DB00915
| DrugBank2 = DBSALT000203
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2045 | ChemSpiderID = 2045
| ChemSpiderID2 = 57724
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BF4C9Z1J53 | UNII = BF4C9Z1J53
| UNII2 = M6Q1EO9TD0
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07441 | KEGG = D07441
| KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = D00777
| ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2618 | ChEBI = 2618
| ChEBI2 = 2619
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 660 | ChEMBL = 660
| ChEMBL2 = 1569
| NIAID_ChemDB =
| PDB_ligand =
<!-- | Beilstein = 2204333 -->
<!-- | Gmelin = 27066 -->
<!-- | HMDB = HMDB0015051 -->
<!-- | EINECS = 212-201-2 -->
| synonyms = 1-Adamantylamine; 1-Adamantanamine; 1-Aminoadamantane; Midantane; Midantan


<!--Chemical data--> <!-- Chemical data -->
| IUPAC_name = Adamantan-1-amine
| C=10 | H=17 | N=1
| C=10 | H=17 | N=1
| molecular_weight = 151.249 g/mol
| smiles = NC13CC2CC(CC(C1)C2)C3 | SMILES = C1C2CC3CC1CC(C2)(C3)N
| InChI = 1/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2
| InChIKey = DKNWSYNQZKUICI-UHFFFAOYAJ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2 | StdInChI = 1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DKNWSYNQZKUICI-UHFFFAOYSA-N | StdInChIKey = DKNWSYNQZKUICI-UHFFFAOYSA-N

| synonyms = 1-Adamantylamine
<!-- Physical data -->
| density =
| density_notes =
| melting_point = 180
| melting_high =
| melting_notes = <ref name=r1>{{cite book | editor= Haynes, William M. | date = 2016| title = ] | edition = 97th | publisher = ] | isbn = 9781498754293|page=3.524}}</ref>
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}
<!-- Definition and medical uses -->
'''Amantadine''', sold under the brand name '''Gocovri''' among others, is a ] used to treat ] associated with ] and ], though its use for the latter is no longer recommended because of widespread ].<ref name="CDC_2019" /><ref name="WHO_2011" /> It is also used for a variety of other uses. The drug is taken ].


<!-- Side effects, precautions, and contraindications -->
'''Amantadine''' is the ] known formally as '''1-adamantylamine''' or '''1-aminoadamantane'''. The molecule consists of ] backbone that has an ] group substituted at one of the four ] positions. This ] is sold under the name '''Symmetrel''' for use both as an ] and an antiparkinsonian drug. ] is a closely related derivative of adamantane with similar biological properties.
Amantadine has a mild ] profile. Common neurological side effects include ], ], ], and ].<ref name="Chang_2020">{{cite book | vauthors = Chang C, Ramphul K | chapter = Amantadine |date=2020 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK499953/ | title = StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29763128|access-date=2 November 2020}}</ref> Because of its effects on the ] (CNS), it should be combined cautiously with additional CNS ]s or ] drugs. Given that it is ], amantadine is contraindicated in persons with ].<ref name="Gocovri FDA label2">{{cite web|date=26 December 2019|title=Gocovri- amantadine capsule, coated pellets|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82ff865f-78f3-4c94-b6a9-727a54944b28|access-date=22 January 2020|website=DailyMed}}</ref> Due to its anticholinergic effects, it should be taken with caution by those with ]s or ].<ref name="FDA_2019">{{Cite web|title=Symmetrel (Amantadine Hydrochloride, USP) fact sheet|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/016023s041,018101s016lbl.pdf|access-date=28 July 2019|website=U.S. ] (FDA) }}</ref>


<!-- Mechanism of action and chemistry -->
Apart from medical uses, this compound is useful as a building block, allowing the insertion of an ].
The ] of amantadine is complex.<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /> It acts as a ] ], ], ], and weak ], among other actions.<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /> The precise ] of its therapeutic effects in the treatment of CNS disorders is unclear.<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /> The ] mechanism of action is inhibition of the influenza virus A ], which prevents endosomal escape (i.e., the release of viral genetic material into the host cytoplasm).<ref>{{cite book |vauthors=James SH, Whitley RJ | chapter = Influenza Viruses|date=2017 |title=Infectious Diseases |pages=1465–1471.e1 |publisher=Elsevier |doi=10.1016/b978-0-7020-6285-8.00172-6 |isbn=978-0-7020-6285-8}}</ref><ref>{{cite journal |vauthors=Balgi AD, Wang J, Cheng DY, Ma C, Pfeifer TA, Shimizu Y, Anderson HJ, Pinto LH, Lamb RA, DeGrado WF, Roberge M |title=Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay |journal=PLOS ONE |volume=8 |issue=2 |pages=e55271 |date=1 February 2013 |pmid=23383318 |pmc=3562233 |doi=10.1371/journal.pone.0055271 |bibcode=2013PLoSO...855271B |veditors=Bouvier NM |doi-access=free}}</ref> Amantadine is an ] ] and is related to ] and ].<ref name="RagshaniyaKumarTittal2024">{{cite journal | vauthors = Ragshaniya A, Kumar V, Tittal RK, Lal K | title = Nascent pharmacological advancement in adamantane derivatives | journal = Arch Pharm (Weinheim) | volume = 357 | issue = 3 | pages = e2300595 | date = March 2024 | pmid = 38128028 | doi = 10.1002/ardp.202300595 | url = }}</ref>


<!-- History, society, and culture -->
According to the US ], 100% of seasonal ] and ] samples tested have shown resistance to adamantanes, and amantadine is no longer recommended for treatment of influenza. Additionally, its effectiveness as an antiparkinsonian drug is controversial, with a 2003 ] concluding that it was ineffective for this purpose.<ref name="Cochrane report">{{cite journal | doi = 10.1002/14651858.CD003468 | title = Amantadine in Parkinson's disease | journal = Cochrane Database of Systematic Reviews | year = 2003 | last1 = Crosby | first1 = Niall J | last2 = Deane | first2 = Katherine | last3 = Clarke | first3 = Carl E | editor1-last = Clarke | editor1-first = Carl E}}</ref>
Amantadine was first used for the treatment of ].<ref name="DanyszDekundyScheschonka2021" /> After its antiviral properties were initially reported in 1963, amantadine received approval for ] against the influenza virus A in 1966.<ref name="DanyszDekundyScheschonka2021" /><ref name="Hubsher_2012">{{cite journal|vauthors=Hubsher G, Haider M, Okun MS|date=April 2012|title=Amantadine: the journey from fighting flu to treating Parkinson disease|journal=Neurology|volume=78|issue=14|pages=1096–9|doi=10.1212/WNL.0b013e31824e8f0d|pmid=22474298|s2cid=21515610}}</ref> In 1968, its antiparkinsonian effects were serendipitously discovered.<ref name="DanyszDekundyScheschonka2021" /> In 1973, the ] (FDA) approved amantadine for use in the treatment of ].<ref name="DanyszDekundyScheschonka2021" /> In 2020, the ] was approved for use in the treatment of ].<ref name="DanyszDekundyScheschonka2021" /><ref>{{cite journal | vauthors = Hauser RA, Lytle J, Formella AE, Tanner CM | title = Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson's disease | journal = npj Parkinson's Disease | volume = 8 | issue = 1 | pages = 29 | date = March 2022 | pmid = 35304480 | pmc = 8933492 | doi = 10.1038/s41531-022-00291-1 }}</ref>


==History== ==Medical uses==
Amantadine was initially developed to prevent replication of the influenza A virus.<ref name="Raupp-BarcaroVitalGalduróz2018" /> Its main clinical use today is treatment of ].<ref name="Raupp-BarcaroVitalGalduróz2018" /> Other uses include treatment of drug-induced ], motor fluctuations during ] therapy in Parkinson's disease, ], and ]s.<ref name="Raupp-BarcaroVitalGalduróz2018" />
Amantadine was approved by the U.S. ] in October 1966 as a ] agent against Asian influenza and eventually received approval for the treatment of ]<ref>David A. Hounshell and John Kenly Smith, , 1988, Cambridge University Press, p. 469.</ref><ref> (Last accessed May 19, 2008.) October 5, 1982, ].</ref><ref>{{cite journal|doi=10.1126/science.386515|title=Panel urges wide use of antiviral drug|year=1979|last1=Maugh|first1=T.|journal=Science|volume=206|pages=1058–60|pmid=386515|issue=4422}}</ref><ref>{{cite journal|doi=10.1126/science.192.4235.130|title=Amantadine: an Alternative for Prevention of Influenza|year=1976|last1=Maugh|first1=T. H.|journal=Science|volume=192|pages=130–1|pmid=17792438|issue=4235}}</ref> in adults. In 1969, the drug was also discovered by accident to help reduce symptoms of ], drug-induced ] syndromes and ].


===Parkinson's disease===
==Indications==
Amantadine is used to treat Parkinson's disease-related ] and drug-induced parkinsonism syndromes.<ref name="rascol">{{cite journal | vauthors = Rascol O, Fabbri M, Poewe W | title = Amantadine in the treatment of Parkinson's disease and other movement disorders | journal = The Lancet. Neurology | volume = 20 | issue = 12 | pages = 1048–1056 | date = December 2021 | pmid = 34678171 | doi = 10.1016/s1474-4422(21)00249-0 | s2cid = 239031883 }}</ref> Amantadine may be used alone or in combination with another anti-Parkinson's or ] drug.<ref name="Golan_2017">{{Cite book|title=Principles of pharmacology: the pathophysiologic basis of drug therapy|vauthors=Golan DE, Armstrong EJ, Armstrong AW|publisher=Wolters Kluwer|year=2017|isbn=9781451191004|edition=4th|location=Philadelphia|pages=142, 199, 205t, 224t, 608, 698–700|oclc=914593652}}</ref> The specific symptoms targeted by amantadine therapy are dyskinesia and rigidity.<ref name=rascol/> The ] amantadine formulation is commonly used to treat dyskinesias in people receiving ] therapy for Parkinson's disease.<ref name=rascol/> A 2003 ] had concluded evidence was insufficient to prove the safety or efficacy of amantadine to treat dyskinesia.<ref>{{cite journal | vauthors = Crosby NJ, Deane KH, Clarke CE | title = Amantadine for dyskinesia in Parkinson's disease | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD003467 | date = 22 April 2003 | volume = 2010 | pmid = 12804468 | doi = 10.1002/14651858.CD003467 | pmc = 8715285 | collaboration = Cochrane Movement Disorders Group }}</ref>
===Parkinson===
As an antiparkinsonian it can be used as monotherapy; or together with ] to treat L-DOPA-related motor fluctuations (i.e., shortening of L-DOPA duration of clinical effect, probably related to progressive neuronal loss) and L-DOPA-related dyskinesias (] movements associated with long-term L-DOPA use, probably related to chronic pulsatile stimulation of ] receptors).


In 2008, the ] (WHO) reported amantadine is not effective as a stand-alone parkinsonian therapy, but recommended it could be used in combination therapy with levodopa.<ref name="WHO Formulary 2008">{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-9241547659 | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | publisher = ] (WHO) |page = 242 | hdl-access = free }}</ref>
Contrary to its continued use, a 2003 Cochrane review of the scientific literature concluded that there is inadequate evidence to support the use of amantadine for Parkinson's.<ref name="Cochrane report"/>


===Influenza=== ===Influenza A===
Amantadine is not recommended for treatment or ] of influenza A in the United States.<ref name="CDC_2019">{{Cite web|url=https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm|title=Influenza Antiviral Medications: Summary for Clinicians |date=17 April 2019|website=U.S. ] (CDC) |access-date=14 July 2019}}</ref> Amantadine has no effect preventing or treating ] infections.<ref name="CDC_2019" /> The US ] (CDC) found 100% of seasonal ] and 2009 ] flu samples were resistant to adamantanes (amantadine and rimantadine) during the 2008–2009 flu season.<ref name="Golan_2017" /><ref name="cdc weekly report">{{cite web | title=Seasonal Influenza (Flu) – Weekly Report: Influenza Summary Update | website=U.S. ] (CDC) | date=5 September 2009 | url=https://www.cdc.gov/flu/weekly/weeklyarchives2008-2009/weekly35.htm }}</ref>
Amantadine is no longer recommended for treatment of influenza B infection.


The U.S. CDC guidelines recommend only ]s for influenza treatment and prophylaxis.{{medcn|date=February 2022}} The CDC recommends against amantadine and rimantadine to treat influenza A infections.<ref name="CDC_2019" />
For the 2008/2009 flu season, the United States' ] (CDC) found that 100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to adamantanes.<ref name="cdc weekly report">, cdc.gov</ref> The CDC issued an alert to doctors to prescribe the ]s ] and ] instead of amantadine and rimantadine for treatment of current circulating flu.<ref>{{cite web |url= http://www.cdc.gov/flu/han011406.htm|title= CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season|accessdate=2008-05-20|date= 2006-01-14|work= CDC Health Alert|publisher=]}}</ref><ref name="JIDResistance">{{cite journal

|last =Deyde
Similarly, the 2011 WHO virology report showed all tested H1N1 influenza A viruses were resistant to amantadine.<ref name="WHO_2011">{{Cite web|url=https://www.who.int/influenza/gisrs_laboratory/updates/antiviral_susceptibility/en/|archive-url=https://web.archive.org/web/20170727081143/http://www.who.int/influenza/gisrs_laboratory/updates/antiviral_susceptibility/en/|url-status=dead|archive-date=27 July 2017|title=Summary of influenza antiviral susceptibility surveillance findings|date=September 2010 – March 2011|website=] (WHO)|access-date=19 July 2019}}</ref> WHO guidelines recommend against use of M2 inhibitors for influenza A.{{medcn|date=February 2022}} The continued high rate of resistance observed in laboratory testing of influenza A has reduced the priority of M2 resistance testing.{{medcn|date=February 2022}}
|first =Varough M.

|coauthors =Xu, Xiyan; Bright, Rick A.; Shaw, Michael; Smith, Catherine B.; Zhang, Ye; Shu, Yuelong; Gubareva, Larisa V.; Cox, Nancy J.; Klimov, Alexander I.
A 2014 Cochrane review did not find evidence for efficacy or safety of amantadine used for the prevention or treatment of influenza A.<ref>{{cite journal | vauthors = Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJ | title = Amantadine and rimantadine for influenza A in children and the elderly | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD002745 | date = November 2014 | volume = 2014 | pmid = 25415374 | pmc = 7093890 | doi = 10.1002/14651858.CD002745.pub4 | doi-access = free | collaboration = Cochrane Acute Respiratory Infections Group }}</ref>
|title =Surveillance of Resistance to Adamantanes among Influenza A(H3N2) and A(H1N1) Viruses Isolated Worldwide

|journal =Journal of Infectious Diseases
===Extrapyramidal symptoms===
|volume =196
An extended-release ] of amantadine is used to treat ] in patients with Parkinson's disease.<ref name="Gocovri FDA label">{{cite web | title=Gocovri- amantadine capsule, coated pellets | website=DailyMed | date=26 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82ff865f-78f3-4c94-b6a9-727a54944b28 | access-date=22 January 2020}}</ref> The WHO recommends the use of amantadine as a combination therapy to reduce levodopa side effects.<ref name="WHO Formulary 2008" />
|issue =2
|pages =249–257
|year = 2007 |doi =10.1086/518936
|pmid =17570112 }}</ref>


===Off-label uses=== ===Off-label uses===
====Fatigue in multiple sclerosis====
Amantadine is frequently used to treat the chronic ] often experienced by patients with ].<ref>{{cite journal|pmid=2730380|year=1989|last1=Cohen|first1=RA|last2=Fisher|first2=M|title=Amantadine treatment of fatigue associated with multiple sclerosis|volume=46|issue=6|pages=676–80|journal=Archives of neurology}}</ref> Additionally, there have been anecdotal reports that low-dose amantadine has been successfully used to treat ].<ref>Hallowell, Edward M. and John J. Ratey, ''Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder'' (2005), pp. 253-5 ISBN 0-345-44230-X</ref> Limited data has shown that amantadine may help to relieve ].<ref>{{cite journal |author=Shrivastava RK, Shrivastava S, Overweg N, Schmitt M |title=Amantadine in the treatment of sexual dysfunction associated with selective serotonin reuptake inhibitors |journal=] |volume=15 |issue=1 |pages=83–4 |year=1995 |pmid=7714234 |doi= 10.1097/00004714-199502000-00014}}</ref><ref>{{cite journal |author=Balogh S, Hendricks SE, Kang J |title=Treatment of fluoxetine-induced anorgasmia with amantadine |journal=] |volume=53 |issue=6 |pages=212–3 |year=1992 |pmid=1607353}}</ref><ref>{{cite journal |author=Keller Ashton A, Hamer R, Rosen RC |title=Serotonin reuptake inhibitor-induced sexual dysfunction and its treatment: a large-scale retrospective study of 596 psychiatric outpatients |journal=] |volume=23 |issue=3 |pages=165–75 |year=1997 |pmid=9292832 |doi=10.1080/00926239708403922}}</ref>
A 2007 Cochrane literature review concluded that no overall evidence supports the use of amantadine in treating fatigue in patients with multiple sclerosis (MS).<ref>{{cite journal | vauthors = Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C | title = Amantadine for fatigue in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD002818 | date = January 2007 | volume = 2007 | pmid = 17253480 | pmc = 6991937 | doi = 10.1002/14651858.CD002818.pub2 | collaboration = Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group }}</ref> A follow-up 2012 Cochrane review stated that some amantadine-induced improvement in fatigue may occur in some people with MS.<ref>{{cite journal | vauthors = Payne C, Wiffen PJ, Martin S | title = WITHDRAWN: Interventions for fatigue and weight loss in adults with advanced progressive illness | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD008427 | date = April 2017 | issue = 4 | pmid = 28387447 | doi = 10.1002/14651858.cd008427 | publisher = John Wiley & Sons, Ltd | pmc = 6478103 | place = Chichester, UK }}</ref> Despite multiple control trials that have also demonstrated improvements in subjective and objective ratings of fatigue, no final conclusion has been drawn regarding its effectiveness.<ref>{{cite journal | vauthors = Generali JA, Cada DJ | title = Amantadine: multiple sclerosis-related fatigue | journal = Hospital Pharmacy | volume = 49 | issue = 8 | pages = 710–2 | date = September 2014 | pmid = 25477595 | pmc = 4252198 | doi = 10.1310/hpj4908-710 }}</ref>


Consensus guidelines from the German Multiple Sclerosis Society (GMSS) in 2006 state that amantadine produces moderate improvement in subjective fatigue, problem solving, memory, and concentration. Thus, in 2006, GMSS guidelines recommended the use of amantadine in MS-related fatigue.<ref>{{cite journal | vauthors = Henze T, Rieckmann P, Toyka KV | title = Symptomatic treatment of multiple sclerosis. Multiple Sclerosis Therapy Consensus Group (MSTCG) of the German Multiple Sclerosis Society | journal = European Neurology | volume = 56 | issue = 2 | pages = 78–105 |year = 2006 | pmid = 16966832 | doi = 10.1159/000095699 | s2cid = 5069086 | url = https://www.karger.com/Article/FullText/95699 | doi-access = free }}</ref>
==Adverse effects==
Amantadine has been associated with several ] (CNS) side effects, likely due to amantadine's ] and ] activity, and to a lesser extent, its activity as an ]. CNS side effects include nervousness, anxiety, agitation, insomnia, difficulty in concentrating, and exacerbations of pre-existing ] disorders and ] symptoms in patients with ] or ]. The usefulness of amantadine as an anti-parkinsonian drug is somewhat limited by the need to screen patients for a history of seizures and psychiatric symptoms.


In the UK, NICE recommends considering amantadine for MS fatigue.<ref>{{cite web | url=https://www.nice.org.uk/guidance/ng220/chapter/recommendations#ms-symptom-management-and-rehabilitation | title=Recommendations &#124; Multiple sclerosis in adults: Management &#124; Guidance &#124; NICE | date=22 June 2022 }}</ref>
Rare cases of severe skin rashes such as ]<ref>K C Singhal & S Z Rahman, Stevens Johnson Syndrome induced by Amantadine, Rational Drug Bulletin, 2002, Vol. 12, No. 1: 6</ref> and ] in patients treated with amantadine have also been reported.<ref name="EndoPharmRXInfo">{{cite journal
|author =]
|title =Symmetrel (Amantadine) Prescribing Information
|date =May 2003
|url =http://www.symmetrel.com/PDF/symmetrel_pack_insert.pdf
|format =PDF
|accessdate =2007-08-02}}</ref><ref>{{cite journal|pmid=3791133|year=1986|last1=Cook|first1=PE|last2=Dermer|first2=SW|last3=McGurk|first3=T|title=Fatal overdose with amantadine|volume=31|issue=8|pages=757–8|journal=Canadian Journal of Psychiatry}}</ref>


====Disorders of consciousness====
] is a possible side effect of amantadine use for ].<ref>{{cite journal | pmc = 1796527 | pmid=5580722 | volume=2 | issue=5762 | title=Livedo reticularis during amantadine treatment | year=1971 | month=June | pages=627–8 | author=Vollum DI, Parkes JD, Doyle D}}</ref>
] (DoC) include ], ] (VS), and minimally conscious state (MCS). Amantadine has been shown to increase the rate of emergence from a MCS, defined by consistent demonstration of interactive communication and functional objective use. In ] patients in the ], amantadine has also been shown in various randomized control trials to increase the rate of functional recovery and arousal, particularly in the time period immediately following an injury.<ref name="Ma_2020">{{cite journal | vauthors = Ma HM, Zafonte RD | title = Amantadine and memantine: a comprehensive review for acquired brain injury | journal = Brain Injury | volume = 34 | issue = 3 | pages = 299–315 | date = February 2020 | pmid = 32078407 | doi = 10.1080/02699052.2020.1723697 | s2cid = 211232548 }}</ref> Also, significantly improved consciousness has been reported in patients treated for nontraumatic cases of DoC, such as in the case of a ], ], and ].<ref>{{cite journal | vauthors = Gao Y, Ma L, Liang F, Zhang Y, Yang L, Liu X, Yang J | title = The use of amantadine in patients with unresponsive wakefulness syndrome after severe cerebral hemorrhage | journal = Brain Injury | volume = 34 | issue = 8 | pages = 1084–1088 | date = July 2020 | pmid = 32552090 | doi = 10.1080/02699052.2020.1780315 | s2cid = 219909194 }}</ref> In 2018, the ] <!-- (AAN) --> updated treatment guidelines on the use of amantadine for patients with prolonged DoC, recommending the use of amantadine (100–200{{nbsp}}mg b.i.d.) for adults with DoC 4 to 16 weeks after injury to support early functional recovery and reduce disability.<ref>{{cite journal | vauthors = Giacino JT, Katz DI, Schiff ND, Whyte J, Ashman EJ, Ashwal S, Barbano R, Hammond FM, Laureys S, Ling GS, Nakase-Richardson R, Seel RT, Yablon S, Getchius TS, Gronseth GS, Armstrong MJ | title = Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research | journal = Neurology | volume = 91 | issue = 10 | pages = 450–460 | date = September 2018 | pmid = 30089618 | doi = 10.1212/WNL.0000000000005926 | pmc = 6139814 }}</ref>


====Brain injury recovery====
==Physical and chemical properties==
In various studies, amantadine and ] have been shown to accelerate the rate of recovery from a brain injury.<ref name="auto">{{cite journal | vauthors = Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, Eifert B, Long D, Katz DI, Cho S, Yablon SA, Luther M, Hammond FM, Nordenbo A, Novak P, Mercer W, Maurer-Karattup P, Sherer M | title = Placebo-controlled trial of amantadine for severe traumatic brain injury | journal = The New England Journal of Medicine | volume = 366 | issue = 9 | pages = 819–26 | date = March 2012 | pmid = 22375973 | doi = 10.1056/NEJMoa1102609 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kafi H, Salamzadeh J, Beladimoghadam N, Sistanizad M, Kouchek M | title = Study of the neuroprotective effects of memantine in patients with mild to moderate ischemic stroke | journal = Iranian Journal of Pharmaceutical Research | volume = 13 | issue = 2 | pages = 591–8 |year = 2014 | pmid = 25237355 | pmc = 4157035 }}</ref> The time-limited window following a brain injury is characterized by ], or the capacity of ]s in the brain to adapt and compensate after injury. Thus, ] often start patients on amantadine as soon as impairments are recognized. Some case reports also show improved functional recovery with amantadine treatment occurring years after the initial brain injury.<ref name="Ma_2020"/> Evidence is insufficient to determine if the functional gains are a result of effects through the ] or ] pathways. Some patients may benefit from direct dopamine stimulation with amantadine, while others may benefit more from other stimulants that act more on the norepinephrine pathway, such as ].<ref name="Ma_2020" /> If treatment with amantadine improves long-term outcomes or simply accelerates recovery is unclear.<ref name="auto"/> Nonetheless, amantadine-induced acceleration of recovery reduces the burden of disability, lessens health-care costs, and minimizes ] stressors in patients.{{cn|date=February 2022}}
===Synthesis===
Amantadine may be prepared by reacting ] with ] or ] to give the bromide or nitroester at position one. Reaction of either compound with ] affords the acetamide, which is hydrolyzed to give 1-adamantylamine:<ref>{{Cite doi|10.1007/BF00757832}}</ref><ref>{{cite journal | author = H. Stetter, J. Mayer, M. Schwarz, K. Wulf | journal = ] | volume = 93 | pages = 226 | year = 1960 | doi = 10.1002/cber.19600930133 | title = Über Verbindungen mit Urotropin-Struktur, XVI. Beiträge zur Chemie der Adamantyl-(1)-Derivate}}</ref><ref>J.C. Watts, P. Marvin, {{US Patent|3310469}} (1967).</ref>


==Contraindications==
]
Amantadine is contraindicated in persons with end-stage kidney disease,<ref name="Gocovri FDA label" /> as the drug is renally cleared.<ref name="TGA" /><ref name="FDA_2019" /><ref name="EndoPharmRXInfo">{{cite web|date=May 2003|title=Symmetrel (Amantadine) Prescribing Information|url=http://www.symmetrel.com/PDF/symmetrel_pack_insert.pdf|url-status=dead|publisher=]|archive-url=https://web.archive.org/web/20141117154734/http://www.symmetrel.com/PDF/symmetrel_pack_insert.pdf|archive-date=17 November 2014|access-date=2 August 2007}}</ref>


Amantadine may have ] side effects. Thus, patients with an enlarged prostate or glaucoma should use with caution.<ref name="Chang_2020" />
==Dosage and mechanism of action==
A starting dose is often 100&nbsp;mg once daily. All influenza B strains, many influenza A strains (and virtually all H1N1 "swine flu" strains) are resistant to amantadine, so a failure at this dose is likely due to resistance and not underdosing. For its anti-Parkinsonian effects, a starting dose of 300&nbsp;mg once daily is normal, but can be increased to a limit of about 400&nbsp;mg.


] are contraindicated while taking amantadine.<ref name="Gocovri FDA label" /> Amantadine might inhibit viral replication and reduce the efficacy of administered vaccines. The U.S. ] recommends avoiding amantadine for two weeks prior to vaccine administration and 48 hours afterward.<ref name="FDA_2019" />
The mechanisms for amantadine's antiviral and antiparkinsonian effects appear to be unrelated.


==Side effects==
*The mechanism of Amantadine's antiviral activity involves interference with a viral protein, ] (an ]),<ref name="pmid7688826">{{cite journal |author=Wang C, Takeuchi K, Pinto LH, Lamb RA |title=Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block |journal=Journal of virology |volume=67 |issue=9 |pages=5585–94 |year=1993 |pmid=7688826 |pmc=237962}}</ref><ref name="pmid18669647">{{cite journal |author=Jing X, Ma C, Ohigashi Y, ''et al.'' |title=Functional studies indicate amantadine binds to the pore of the influenza A virus M2 proton-selective ion channel |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=105 |issue=31 |pages=10967–72 |year=2008|pmid=18669647 |pmc=2492755 |doi=10.1073/pnas.0804958105}}</ref> which is required for the viral particle to become "uncoated" once taken inside a cell by ].
Amantadine is generally ] and has a mild side effect profile.<ref>{{cite journal | vauthors = Hosenbocus S, Chahal R | title = Amantadine: a review of use in child and adolescent psychiatry | journal = Journal of the Canadian Academy of Child and Adolescent Psychiatry | volume = 22 | issue = 1 | pages = 55–60 | date = February 2013 | pmid = 23390434 | pmc = 3565716 }}</ref>


===Neurological===
*The mechanism of its antiparkinsonian effect is poorly understood. The drug has many effects in the brain, including release of ] and ] from ] endings. It appears to be a weak ]<ref name="Kornhuber1991">Kornhuber J, Bormann J, Hübers M, Rusche K, Riederer P (1991) "Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study." Eur.J.Pharmacol.Mol.Pharmacol.Sect. '''206''':297-300.</ref><ref name="pmid15800186">{{cite journal |author=Blanpied TA, Clarke RJ, Johnson JW |title=Amantadine inhibits NMDA receptors by accelerating channel closure during channel block |journal=Journal of Neuroscience |volume=25 |issue=13 |pages=3312–22 |year=2005 |pmid=15800186 |doi=10.1523/JNEUROSCI.4262-04.2005}}</ref> as well as an ].
Side effects include drowsiness (especially while driving), lightheadedness, falls, and dizziness.<ref name="Gocovri FDA label" /> Patients on amantadine should avoid combination with other CNS-depressing agents, such as alcohol. Excessive alcohol usage may increase the potential for CNS effects such as dizziness, confusion, and light-headedness.<ref name="Chang_2020" />


Rare severe adverse effects include ], depression, convulsions, ], and suicidal ideation.<ref name="Chang_2020" /> It has also been associated with disinhibited actions (gambling, sexual activity, spending, other addictions) and diminished control over compulsions.<ref name="Gocovri FDA label" />
Amantadine appears to act through several pharmacological mechanisms, but no dominant mechanism of action has been identified. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels.{{Citation needed|date=April 2010}}


Amantadine may cause ], feeling overexcited, hallucinations, and nightmares.<ref>Amantadine Hydrochloride package leaflet, Manx Healthcare, 1/24; Common possible side effects (may affect up to one in 10 people)</ref>
==Veterinary misuse==

In 2005, Chinese poultry farmers were reported to have used amantadine to protect birds against ].<ref name="WashPostBirdFlu">{{cite news
===Cardiovascular===
|last =Sipress
Amantadine may cause orthostatic hypotension, syncope, and peripheral edema.<ref name="Gocovri FDA label" />
|first =Alan

|title =Bird Flu Drug Rendered Useless
===Gastrointestinal===
|pages =A01
Amantadine has also been associated with dry mouth and constipation.<ref name="Gocovri FDA label" />
|publisher =]

|date =2005-06-18
===Skin===
|url =http://www.washingtonpost.com/wp-dyn/content/article/2005/06/17/AR2005061701214.html
Rare cases of skin rashes, such as ] and ] have also been reported in patients treated with amantadine.<ref>{{cite journal | vauthors = Bahrani E, Nunneley CE, Hsu S, Kass JS | title = Cutaneous Adverse Effects of Neurologic Medications | journal = CNS Drugs | volume = 30 | issue = 3 | pages = 245–67 | date = March 2016 | pmid = 26914914 | doi = 10.1007/s40263-016-0318-7 | s2cid = 10560952 | url = http://link.springer.com/10.1007/s40263-016-0318-7 }}</ref><ref>{{cite journal | vauthors = Vollum DI, Parkes JD, Doyle D | title = Livedo reticularis during amantadine treatment | journal = British Medical Journal | volume = 2 | issue = 5762 | pages = 627–8 | date = June 1971 | pmid = 5580722 | pmc = 1796527 | doi = 10.1136/bmj.2.5762.627 }}</ref>
|accessdate =2007-08-02}}</ref> In Western countries and according to international livestock regulations, amantadine is approved only for use in humans. Chickens in China have received an estimated 2.6 billion doses of amantadine.<ref name="WashPostBirdFlu"/> Avian flu (]) strains in China and southeast Asia are now resistant to amantadine, although strains circulating elsewhere still seem to be sensitive. If amantadine-resistant strains of the virus spread, the drugs of choice in an avian flu outbreak will probably be restricted to the scarcer and costlier ] and ], which work by a different mechanism and are less likely to trigger resistance.

===Kidney===
Amantadine inhibits the kidney's active-transport removal and transfer of creatinine from blood to urine, which normally occurs in the proximal tubules of the nephrons. The active-transport removal mechanism accounts for about 15% of creatinine clearance, so amantadine may increase serum creatinine concentrations 15% above normal levels and give the false impression of mild kidney disease in patients whose kidneys are actually undamaged (because kidney function is often assessed by measuring the concentration of creatinine in blood.) Also, if the patient does have kidney disease, amantadine may cause it to appear as much as 15% worse than it actually is.<ref>{{cite web | url=https://medsafe.govt.nz/profs/PUArticles/December2019/Some-medicines-increase-serum-creatinine-without-affecting-glomerular-function.htm | title=Some medicines increase serum creatinine without affecting glomerular function }}</ref>

===Pregnancy and lactation===
Amantadine is USFDA category C for pregnancy. ] effects have been observed in humans (case reports) and animal reproduction studies. Amantadine may also be present in ] and negatively alter breast milk production or excretion. The decision to breastfeed during amantadine therapy should consider the risk of infant exposure, the benefits of breastfeeding, and the benefits of the drug to the mother.<ref name="Chang_2020" />

==Interactions==
Amantadine may affect the CNS because of its dopaminergic and anticholinergic properties. The mechanisms of action are not fully known. Because of the CNS effects, caution is required when prescribing additional CNS stimulants or anticholinergic drugs.<ref name="FDA_2019" /> Thus, concurrent use of alcohol with amantadine is not recommended because of enhanced CNS depressant effects.<ref>Gocovri (amantadine) extended-release capsules . Emeryville, CA: Adamas Pharma, LLC; August 2017</ref> In addition, antidopaminergic drugs such as ] and ]s should be avoided.<ref>Reglan (metoclopramide) . Baudette, MN: ANI Pharmaceuticals Inc; August 2017</ref><ref>{{cite journal | vauthors = Tarsy D, Parkes JD, Marsden CD | title = Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 38 | issue = 4 | pages = 331–335 | date = April 1975 | pmid = 1095689 | pmc = 491929 | doi = 10.1136/jnnp.38.4.331 }}</ref> These interactions are likely related to opposing dopaminergic mechanisms of action, which inhibits amantadine's anti-Parkinson effects.{{medcn|date=February 2022}}

==Pharmacology==
===Mechanism of action===
====Central nervous system disorders====
The ] of the antiparkinsonian effects of amantadine is poorly understood.<ref>{{Cite web|title=Amantadine – MeSH|url=https://www.ncbi.nlm.nih.gov/mesh/68000547|publisher=NCBI}}</ref> The effects of amantadine in Parkinson's disease were originally assumed to be ] or ], but the situation soon proved more complicated than this.<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /> The ] of amantadine are complex, and it interacts with many different ]s at a variety of concentrations and hence ].<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" />

The drug is a weak ], ], and ].<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /><ref name="Austria-Codex">{{cite book|title=Austria-Codex|publisher=Österreichischer Apothekerverlag|year=2007|isbn=978-3-85200-181-4|editor=Jasek, W|edition=62nd|location=Vienna|page=3962|language=de}}</ref><ref name="Kornhuber1991">{{cite journal|vauthors=Kornhuber J, Bormann J, Hübers M, Rusche K, Riederer P|date=April 1991|title=Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study|journal=European Journal of Pharmacology|volume=206|issue=4|pages=297–300|doi=10.1016/0922-4106(91)90113-v|pmid=1717296}}</ref><ref name="pmid15800186">{{cite journal|vauthors=Blanpied TA, Clarke RJ, Johnson JW|date=March 2005|title=Amantadine inhibits NMDA receptors by accelerating channel closure during channel block|journal=The Journal of Neuroscience|volume=25|issue=13|pages=3312–22|doi=10.1523/JNEUROSCI.4262-04.2005|pmc=6724906|pmid=15800186}}</ref> It is a ] of the ]s, specifically the ] and ]s.<ref name="DanyszDekundyScheschonka2021" />

In 1993, amantadine was found to bind to the ] with relatively high ] (K<sub>i</sub> = 20.25{{nbsp}}μM).<ref name="DanyszDekundyScheschonka2021" /><ref name="KornhuberSchoppmeyerRiederer1993">{{cite journal | vauthors = Kornhuber J, Schoppmeyer K, Riederer P | title = Affinity of 1-aminoadamantanes for the sigma binding site in post-mortem human frontal cortex | journal = Neurosci Lett | volume = 163 | issue = 2 | pages = 129–131 | date = December 1993 | pmid = 8309617 | doi = 10.1016/0304-3940(93)90362-o | url = }}</ref> In 2004, it was discovered that amantadine and memantine bind to and act as ]s of the ] (K<sub>i</sub> = 7.44{{nbsp}}μM and 2.60{{nbsp}}μM, respectively) and that activation of the σ<sub>1</sub> receptor is potentially involved in the dopaminergic effects of amantadine at therapeutically relevant concentrations.<ref name="PeetersRomieu2004">{{cite journal|vauthors=Peeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E|date=April 2004|title=Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine|journal=The European Journal of Neuroscience|volume=19|issue=8|pages=2212–20|doi=10.1111/j.0953-816X.2004.03297.x|pmid=15090047|s2cid=19479968}}</ref> σ<sub>1</sub> receptor activation is one of amantadine's more potent actions.<ref name="DanyszDekundyScheschonka2021" /><ref name="PeetersRomieu2004" /> σ<sub>1</sub> receptor agonists enhance ] activity, modulate ]-stimulated dopamine release, increase dopamine release in the ] '']'', and decrease dopamine ].<ref name="DanyszDekundyScheschonka2021" /> As such, σ<sub>1</sub> receptor activation may be involved in the antiparkinsonian and other central nervous system effects of amantadine.<ref name="DanyszDekundyScheschonka2021" /><ref name="PeetersRomieu2004" />

Binding of amantadine to the NMDA receptor was first reported in 1989, and antagonism of the receptor was first reported in 1991.<ref name="DanyszDekundyScheschonka2021" /> Despite some reports, the NMDA receptor antagonism of amantadine is probably not its primary mechanism of action.<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /> It occurs at relatively high concentrations and many of the effects of amantadine are different from those of NMDA receptor antagonists.<ref name="DanyszDekundyScheschonka2021" /> Some of its effects, such as enhancement of dopamine release in the striatum, are even reversed by NMDA receptor antagonists,<ref name="DanyszDekundyScheschonka2021" /> but NMDA receptor antagonism could still contribute to the effects of amantadine.<ref name="DanyszDekundyScheschonka2021" />

Although some publications have reported that amantadine inhibits ], the drug probably does not actually inhibit this ].<ref name="DanyszDekundyScheschonka2021" /><ref name="HuberDietrichEmrich1999" /><ref>{{cite journal|vauthors=Strömberg U, Svensson TH|date=November 1971|title=Further studies on the mode of action of amantadine|journal=Acta Pharmacologica et Toxicologica|volume=30|issue=3|pages=161–71|doi=10.1111/j.1600-0773.1971.tb00646.x|pmid=5171936}}</ref>

Amantadine shows ]-like ] effects (e.g., ]) in animals at sufficiently high doses.<ref name="HuberDietrichEmrich1999" /><ref name="ShimazuTakahataKatsuki2001">{{cite journal | vauthors = Shimazu S, Takahata K, Katsuki H, Tsunekawa H, Tanigawa A, Yoneda F, Knoll J, Akaike A | title = (-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release | journal = Eur J Pharmacol | volume = 421 | issue = 3 | pages = 181–189 | date = June 2001 | pmid = 11516435 | doi = 10.1016/s0014-2999(01)01040-8 | url = }}</ref> It has been found to ] and to ].<ref name="HuberDietrichEmrich1999" /><ref name="DanyszDekundyScheschonka2021" /> The concentrations needed for these effects, though, are very high and may not be therapeutically relevant.<ref name="HuberDietrichEmrich1999" /><ref name="DanyszDekundyScheschonka2021" /> It is about 1/25th to 1/50th as potent as amphetamines.<ref name="HuberDietrichEmrich1999" /> Amantadine has been found to increase dopamine levels in the striatum.<ref name="HuberDietrichEmrich1999" /><ref name="DanyszDekundyScheschonka2021" /> It does not act as a ].<ref name="ShimazuTakahataKatsuki2001" /><ref name="YonedaMotoSakae2001">{{cite journal | vauthors = Yoneda F, Moto T, Sakae M, Ohde H, Knoll B, Miklya I, Knoll J | title = Structure-activity studies leading to (-)1-(benzofuran-2-yl)-2-propylaminopentane, ((-)BPAP), a highly potent, selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain | journal = Bioorg Med Chem | volume = 9 | issue = 5 | pages = 1197–1212 | date = May 2001 | pmid = 11377178 | doi = 10.1016/s0968-0896(01)00002-5 | url = }}</ref><ref name="KnollYonedaKnoll1999">{{cite journal | vauthors = Knoll J, Yoneda F, Knoll B, Ohde H, Miklya I | title = (-)1-(Benzofuran-2-yl)-2-propylaminopentane, , a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain | journal = Br J Pharmacol | volume = 128 | issue = 8 | pages = 1723–1732 | date = December 1999 | pmid = 10588928 | pmc = 1571822 | doi = 10.1038/sj.bjp.0702995 | url = }}</ref>

Amantadine is a ], for example of ].<ref name="DanyszDekundyScheschonka2021" />

Amantadine has been found to increase ] <!-- (AADC) --> ].<ref name="DanyszDekundyScheschonka2021" /> This enzyme is responsible for the ] of dopamine from ].<ref name="DanyszDekundyScheschonka2021" /> An imaging study in humans found that amantadine increased AADC activity in the striatum by up to 27%.<ref name="DanyszDekundyScheschonka2021" />

Various additional actions of amantadine have been described.<ref name="DanyszDekundyScheschonka2021" />

====Influenza====
]

]

The mechanisms for amantadine's antiviral and antiparkinsonian effects are unrelated.<ref name="TGA" /><ref name="FDA_2019"/> Amantadine targets the influenza A M2 ion channel protein. The M2 protein's function is to allow the intracellular virus to replicate (M2 also functions as a proton channel for hydrogen ions to cross into the vesicle), and ] newly formed viral proteins to the extracellular space (viral shedding). By blocking the M2 channel, the virus is unable to replicate because of impaired replication, protein synthesis, and exocytosis.<ref>{{Cite web| work = PubChem|title=Amantadine|url=https://pubchem.ncbi.nlm.nih.gov/compound/2130|access-date=29 July 2019| publisher = U.S. Library of Medicine }}</ref>

Amantadine and rimantadine function in a mechanistically identical fashion, entering the barrel of the tetrameric M2 channel and blocking pore function—i.e., proton translocation.<ref name="Golan_2017" />

Resistance to the drug class is a consequence of mutations to the pore-lining ] residues of the channel, preventing both amantadine and rimantadine from binding and inhibiting the channel in their usual way.<ref>{{cite journal | vauthors = Hussain M, Galvin HD, Haw TY, Nutsford AN, Husain M | title = Drug resistance in influenza A virus: the epidemiology and management | journal = Infection and Drug Resistance | volume = 10 | pages = 121–134 | date = 20 April 2017 | pmid = 28458567 | pmc = 5404498 | doi = 10.2147/idr.s105473 | doi-access = free }}</ref>

===Pharmacokinetics===
Amantadine is well-absorbed orally. The onset of action is usually within 48 hours when used for parkinsonian syndromes, including dyskinesia. As plasma concentrations of amantadine increase, the risk for toxicity increases.<ref name="Drugs.com">{{Cite web|title=Amantadine Hydrochloride Monograph for Professionals|url=https://www.drugs.com/monograph/amantadine-hydrochloride.html|access-date=16 November 2020|website=Drugs.com}}</ref><ref name="Drugs.com_2">{{Cite web|title=Amantadine – FDA prescribing information, side effects and uses|url=https://www.drugs.com/pro/amantadine.html|access-date=16 November 2020|website=Drugs.com}}</ref>

Half-life elimination averages eight days in patients with end-stage kidney disease. Amantadine is only minimally removed by ].<ref name="Drugs.com_2" /><ref>{{cite journal | vauthors = Deleu D, Northway MG, Hanssens Y | title = Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease | journal = Clinical Pharmacokinetics | volume = 41 | issue = 4 | pages = 261–309 | date = 2002 | pmid = 11978145 | doi = 10.2165/00003088-200241040-00003 | s2cid = 39359348 }}</ref>

Amantadine is metabolized to a small extent (5–15%) by ]. It is mainly excreted (90%) unchanged in urine by kidney excretion.<ref name="Drugs.com" />

==Chemistry==
Amantadine is the ] 1-adamantylamine or 1-aminoadamantane, which consists of an ] backbone with an ] group substituted at one of the four ]s.<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00915|title=Amantadine|website=drugbank.ca|access-date=13 July 2019}}</ref> ] is a closely related adamantane derivative with similar biological properties;<ref>{{Cite web|url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8865|title=Rimantadine hydrochloride (CHEBI:8865)|website=ebi.ac.uk|access-date=13 July 2019}}</ref> both target the ] of ].<ref name="Golan_2017" />

Amantadine (1-aminoadamantane) is ] to other adamantanes including ] (1-(adamantan-1-yl)propan-1-amine), ] (''N''-(4-bromophenyl)adamantan-2-amine), ] (1-amino-3,5-dimethyladamantane), and ] (1-(1-aminoethyl)adamantane), among others.

==History==
===Influenza A===
Antiviral properties were first reported in 1963 at the University of Illinois Hospital in Chicago. In this amantadine trial study, volunteer college students were exposed to a viral challenge. The group who received amantadine (100 milligrams 18 hours before viral challenge) had less Asia influenza infections than the ] group.<ref name="Hubsher_2012"/> Amantadine received approval for the treatment of ]<ref>{{cite book| vauthors = Hounshell DA, Smith JK |url=https://books.google.com/books?id=6ld0K9VNpmIC|title=Science and Corporate Strategy: Du Pont R&D, 1902–1980 John|publisher=Cambridge University Press|year=1988|isbn=978-0521327671|page=469 }}</ref><ref>{{cite news|date=5 October 1982|title=Sales of flu drug by du Pont unit a 'disappointment'|work=]|location=Wilmington, Delaware|url=https://query.nytimes.com/gst/fullpage.html?sec=health&res=9C02E0D71F38F936A35753C1A964948260|access-date=19 May 2008}}</ref><ref>{{cite journal|vauthors=Maugh TH|date=November 1979|title=Panel urges wide use of antiviral drug|journal=Science|volume=206|issue=4422|pages=1058–60|bibcode=1979Sci...206.1058M|doi=10.1126/science.386515|pmid=386515}}</ref><ref>{{cite journal|vauthors=Maugh TH|date=April 1976|title=Amantadine: an alternative for prevention of influenza|journal=Science|volume=192|issue=4235|pages=130–1|doi=10.1126/science.192.4235.130|pmid=17792438}}</ref> in adults in 1976.<ref name="Hubsher_2012" /> It was first used in ] in 1966. Amantadine was approved by the U.S. Food and Drug Administration in October 1968, as a ] agent against Asian (H2N2) influenza and received approval for prophylactic use for influenza A in 1976.<ref name="Hubsher_2012" /><ref name="Gocovri FDA label2"/><ref>{{Citation|chapter=International Review of Neurobiology|date=2011|chapter-url=http://dx.doi.org/10.1016/b978-0-12-387003-2.00010-0|pages=i–iii|publisher=Elsevier|doi=10.1016/b978-0-12-387003-2.00010-0|isbn=978-0-12-387003-2|access-date=11 November 2020|title=Recent advances in the use of ''Drosophila'' in neurobiology and neurodegeneration|series=International Review of Neurobiology|volume=99}}</ref>

During the 1980 influenza A epidemic, the first amantadine-resistance influenza viruses were reported. The frequency of amantadine resistance among influenza A (]) viruses from 1991 and 1995 was as low as 0.8%. In 2004, the resistance frequency increased to 12.3%. A year later, resistance increase significantly to 96%, 72%, and 14.5% in China, South Korea, and the United States, respectively. By 2006, 90.6% of H3N2 strains and 15.6% of ] were amantadine resistant. A majority of the amantadine-resistant H3N2 isolates (98.2%) was found to contain an S31N mutation in the M2 transmembrane domain that confers resistance to amantadine.<ref name=kumar>{{cite journal | vauthors = Kumar B, Asha K, Khanna M, Ronsard L, Meseko CA, Sanicas M | title = The emerging influenza virus threat: status and new prospects for its therapy and control | journal = Archives of Virology | volume = 163 | issue = 4 | pages = 831–844 | date = April 2018 | pmid = 29322273 | pmc = 7087104 | doi = 10.1007/s00705-018-3708-y }}</ref> Currently, ] resistance is high among circulating influenza A viruses. Thus, they are no longer recommended for treatment of influenza A.<ref>{{Cite web|date=17 April 2019|title=Antiviral Drug Resistance among Influenza Viruses |url=https://www.cdc.gov/flu/professionals/antivirals/antiviral-drug-resistance.htm|access-date=11 November 2020|website=U.S. ] (CDC) }}</ref>

===Parkinson's disease===
An incidental finding in 1969 prompted investigations about amantadine's effectiveness for treating symptoms of Parkinson's disease.<ref name="Hubsher_2012" /> A woman with Parkinson's disease was prescribed amantadine to treat her influenza infection and reported her ] and tremors improved. She also reported that her symptoms worsened after she finished the course of amantadine.<ref name="Hubsher_2012" /> The published case report was not initially corroborated by any other instances by the medical literature or manufacturer data. A team of researchers looked at a group of 10 patients with Parkinson's disease and gave them amantadine. Seven of them showed improvement, which was convincing evidence for the need of a clinical trial, which included 163 patients with Parkinson's disease; 66% experienced subjective or objective reduction of symptoms with a maximum daily dose of 200{{nbsp}}mg.<ref name="Hubsher_2012" /><ref>{{cite journal | vauthors = Schwab RS, England AC, Poskanzer DC, Young RR | title = Amantadine in the treatment of Parkinson's disease | journal = JAMA | volume = 208 | issue = 7 | pages = 1168–1170 | date = May 1969 | pmid = 5818715 | doi = 10.1001/jama.1969.03160070046011 }}</ref> Additional studies followed patients for greater lengths of time and in different combinations of neurological drugs.<ref>{{cite journal|vauthors=Schwab RS, Poskanzer DC, England AC, Young RR|date=November 1972|title=Amantadine in Parkinson's disease. Review of more than two years' experience|journal=JAMA|volume=222|issue=7|pages=792–5|doi=10.1001/jama.222.7.792|pmid=4677928}}</ref> It was found to be a safe drug that could be used over long periods of time with few side effects as monotherapy or in combination with L-dopa or anticholinergic drugs.<ref name="Hubsher_2012" /> By April 1973, the U.S. FDA approved amantadine for use in the treatment of Parkinson's disease.<ref name="FDA_2019"/><ref name="Hubsher_2012" />

In 2017, the U.S. FDA approved the use of amantadine in an extended-release formulation for the treatment of dyskinesia, an adverse effect of levodopa in people with Parkinson's disease.<ref name="FDA20172">{{Cite web| vauthors = Bastings E |title=NDA 208944 Approval Letter |url= https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/208944orig1s000ltr.pdf }}</ref><ref>{{cite web|date=29 June 2018|title=Drug Approval Package: Gocovri (amantadine extended-release)|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208944Orig1s000TOC.cfm|access-date=22 January 2020|website=U.S. ] (FDA) }}</ref>

==Society and culture==
===Names===
Brand names of amantadine include Gocovri, Symadine, and Symmetrel.<ref name="Drugs.com-International">{{cite web | title=Amantadine (International database) | website=Drugs.com | date=5 August 2024 | url=https://www.drugs.com/international/amantadine.html | access-date=12 August 2024}}</ref><ref name="TGA" /><ref>{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682064.html|title=Amantadine: MedlinePlus Drug Information|website=medlineplus.gov|access-date=22 July 2019}}</ref>

===Recreational use===
] of amantadine at supratherapeutic doses has been reported.<ref name="MorrisWallach2014">{{cite journal | vauthors = Morris H, Wallach J | title = From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs | journal = Drug Test Anal | volume = 6 | issue = 7–8 | pages = 614–632 | date = 2014 | pmid = 24678061 | doi = 10.1002/dta.1620 | url = }}</ref> It is a weak ] and is reported to produce ] and ]-like effects in animals and humans at sufficiently high doses.<ref name="MorrisWallach2014" /><ref name="HealGosdenSmith2018">{{cite journal | vauthors = Heal DJ, Gosden J, Smith SL | title = Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans | journal = Neuropharmacology | volume = 142 | issue = | pages = 89–115 | date = November 2018 | pmid = 29427652 | doi = 10.1016/j.neuropharm.2018.01.049 | url = }}</ref><ref name="NicholsonJonesBalster1998">{{cite journal | vauthors = Nicholson KL, Jones HE, Balster RL | title = Evaluation of the reinforcing and discriminative stimulus properties of the low-affinity N-methyl-D-aspartate channel blocker memantine | journal = Behav Pharmacol | volume = 9 | issue = 3 | pages = 231–243 | date = May 1998 | pmid = 9832937 | doi = | url = }}</ref> However, the very long ] of amantadine (>40{{nbsp}}hours) has likely limited its ].<ref name="MorrisWallach2014" /> Recreational use of the related drug memantine has similarly been reported.<ref name="MorrisWallach2014" />

===Veterinary misuse===
In 2005, Chinese poultry farmers were reported to have used amantadine to protect birds against ].<ref name="WashPostBirdFlu">{{cite news | vauthors = Sipress A | title =Bird Flu Drug Rendered Useless | newspaper=] | date =18 June 2005 | url =https://www.washingtonpost.com/wp-dyn/content/article/2005/06/17/AR2005061701214_pf.html | access-date =2 August 2007}}</ref> In Western countries and according to international livestock regulations, amantadine is approved only for use in humans. Chickens in China have received an estimated 2.6 billion doses of amantadine.<ref name="WashPostBirdFlu"/> Avian flu (]) strains in China and southeast Asia are now resistant to amantadine, although strains circulating elsewhere still seem to be sensitive. If amantadine-resistant strains of the virus spread, the drugs of choice in an avian flu outbreak will probably be restricted to ]s ] and ], which block the action of ] enzyme on the surface of influenza virus particles.<ref name=kumar/> Increasing incidence of oseltamivir resistance in circulating influenza strains (e.g., ]) exists, highlighting the need for new anti-influenza therapies.<ref>{{cite journal | vauthors = Aoki FY, Boivin G, Roberts N | title = Influenza virus susceptibility and resistance to oseltamivir | journal = Antiviral Therapy | volume = 12 | issue = 4 Pt B | pages = 603–16 |year = 2007 | doi = 10.1177/135965350701200S04.1 | pmid = 17944268 | s2cid = 25907483 | doi-access = free }}</ref>

In September 2015, the U.S. FDA announced the recall of ] Chip Twists "Chicken in the Middle" dog treats because the product has the potential to be contaminated with amantadine.<ref name="LoC">{{cite web | url= http://www.accessdata.fda.gov/scripts/enforcement/enforce_rpt-Product-Tabs.cfm?action=select&recall_number=V-261-2015&w=09232015&lang=eng | title= Enforcement Report – Week of September 23, 2015 | publisher= U.S. ] (FDA) | access-date= 30 September 2015 | archive-date= 2 October 2015 | archive-url= https://web.archive.org/web/20151002002441/http://www.accessdata.fda.gov/scripts/enforcement/enforce_rpt-Product-Tabs.cfm?action=select&recall_number=V-261-2015&w=09232015&lang=eng | url-status= dead }}</ref>

==Research==
===Depression===
Interest in and study of amantadine in the treatment of ] has arisen.<ref name="HuberDietrichEmrich1999">{{cite journal | vauthors = Huber TJ, Dietrich DE, Emrich HM | title = Possible use of amantadine in depression | journal = Pharmacopsychiatry | volume = 32 | issue = 2 | pages = 47–55 | date = March 1999 | pmid = 10333162 | doi = 10.1055/s-2007-979191 | url = }}</ref><ref name="DeutschenbaurBeckKiyhankhadiv2016">{{cite journal | vauthors = Deutschenbaur L, Beck J, Kiyhankhadiv A, Mühlhauser M, Borgwardt S, Walter M, Hasler G, Sollberger D, Lang UE | title = Role of calcium, glutamate and NMDA in major depression and therapeutic application | journal = Prog Neuropsychopharmacol Biol Psychiatry | volume = 64 | issue = | pages = 325–33 | date = January 2016 | pmid = 25747801 | doi = 10.1016/j.pnpbp.2015.02.015 | url = }}</ref><ref name="Raupp-BarcaroVitalGalduróz2018">{{cite journal | vauthors = Raupp-Barcaro IF, Vital MA, Galduróz JC, Andreatini R | title = Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials | journal = Braz J Psychiatry | volume = 40 | issue = 4 | pages = 449–458 | date = 2018 | pmid = 29898194 | pmc = 6899375 | doi = 10.1590/1516-4446-2017-2393 | url = }}</ref><ref name="DanyszDekundyScheschonka2021">{{cite journal | vauthors = Danysz W, Dekundy A, Scheschonka A, Riederer P | title = Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials | journal = J Neural Transm (Vienna) | volume = 128 | issue = 2 | pages = 127–169 | date = February 2021 | pmid = 33624170 | pmc = 7901515 | doi = 10.1007/s00702-021-02306-2 | url = }}</ref><ref name="ShamabadiAhmadzadeAgamolaei2022">{{cite journal | vauthors = Shamabadi A, Ahmadzade A, Aqamolaei A, Mortazavi SH, Hasanzadeh A, Akhondzadeh S | title = Ketamine and Other Glutamate Receptor Modulating Agents for Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials | journal = Iran J Psychiatry | volume = 17 | issue = 3 | pages = 320–340 | date = July 2022 | pmid = 36474699 | pmc = 9699814 | doi = 10.18502/ijps.v17i3.9733 | url = }}</ref> A 2017 ] of ] ] for treatment of ] found two ] of amantadine for augmenting ] and found that it was effective.<ref name="KleeblattBetzlerKilarski2017">{{cite journal | vauthors = Kleeblatt J, Betzler F, Kilarski LL, Bschor T, Köhler S | title = Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence | journal = Eur Neuropsychopharmacol | volume = 27 | issue = 5 | pages = 423–441 | date = May 2017 | pmid = 28318897 | doi = 10.1016/j.euroneuro.2017.03.003 | url = }}</ref> However, the ] was very low and no conclusions could be drawn about its effectiveness.<ref name="KleeblattBetzlerKilarski2017" /> A 2022 systematic review of ]s of glutamatergic agents for ] identified one ] of amantadine for this use.<ref name="ShamabadiAhmadzadeAgamolaei2022" /> Amantadine was found to be effective in treating depressive symptoms in the trial.<ref name="ShamabadiAhmadzadeAgamolaei2022" /> The mechanism of action of amantadine in the treatment of depression is unclear, but various mechanisms have been postulated.<ref name="Raupp-BarcaroVitalGalduróz2018" /><ref name="DeutschenbaurBeckKiyhankhadiv2016" /> These include ] actions like indirect enhancement of ] ], ], and ] interactions, ] actions, ] actions such as ], and ], among many others.<ref name="Raupp-BarcaroVitalGalduróz2018" /><ref name="DeutschenbaurBeckKiyhankhadiv2016" /><ref name="HuberDietrichEmrich1999" />

===Attention deficit hyperactivity disorder===
Amantadine has been studied in the treatment of ] (ADHD).<ref name="PozziBertellaGatti2020">{{cite journal | vauthors = Pozzi M, Bertella S, Gatti E, Peeters GG, Carnovale C, Zambrano S, Nobile M | title = Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD) | journal = Expert Opin Emerg Drugs | volume = 25 | issue = 4 | pages = 395–407 | date = December 2020 | pmid = 32938246 | doi = 10.1080/14728214.2020.1820481 | url = | hdl = 2434/851076 | hdl-access = free }}</ref> A 2010 randomized clinical trial showed similar improvements in ADHD symptoms in children treated with amantadine as in those treated with ], with less frequent side effects.<ref name="MohammadiKazemiZia2010">{{cite journal | vauthors = Mohammadi MR, Kazemi MR, Zia E, Rezazadeh SA, Tabrizi M, Akhondzadeh S | title = Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial | journal = Human Psychopharmacology | volume = 25 | issue = 7–8 | pages = 560–565 | date = November 2010 | pmid = 21312290 | doi = 10.1002/hup.1154 | s2cid = 30677758 }}</ref> A 2021 retrospective study showed that amantadine may serve as an effective adjunct to stimulants for ADHD-related symptoms and appears to be a safer alternative to second- or third-generation ]s.<ref>{{cite journal | vauthors = Morrow K, Choi S, Young K, Haidar M, Boduch C, Bourgeois JA | title = Amantadine for the treatment of childhood and adolescent psychiatric symptoms | journal = Proceedings | volume = 34 | issue = 5 | pages = 566–570 | date = September 2021 | pmid = 34456474 | doi = 10.1080/08998280.2021.1925827 | pmc = 8366930 }}</ref>

===COVID-19===
Amantadine has been studied in the treatment of ].<ref name="Płusa2021">{{cite journal | vauthors = Płusa T | title = Przeciwzapalne działanie amantadyny i memantyny w zakażeniu SARS-CoV-2 | trans-title = Anti-inflammatory effects of amantadine and memantine in SARS-CoV-2 infection | language = Polish | journal = Pol Merkur Lekarski | volume = 49 | issue = 289 | pages = 67–70 | date = February 2021 | pmid = 33713098 | doi = | url = https://medpress.com.pl/pubmed.php?article=28967}}</ref><ref name="MarinescuMarinescuMogoantă2020">{{cite journal | vauthors = Marinescu I, Marinescu D, Mogoantă L, Efrem IC, Stovicek PO | title = SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine | journal = Rom J Morphol Embryol | volume = 61 | issue = 4 | pages = 1007–1022 | date = 2020 | pmid = 34171050 | pmc = 8343601 | doi = 10.47162/RJME.61.4.03 | url = }}</ref>


==References== ==References==
{{Reflist|2}} {{Reflist}}


==See also== ==External links==
{{Commonscat}}
*]
*]


{{RNA antivirals}}
{{Influenza}}
{{Antiparkinson}} {{Antiparkinson}}
{{Dopaminergics}} {{Influenza}}
{{Glutamatergics}} {{RNA antivirals}}
{{Stimulants}}
{{Navboxes
| title = ]
| titlestyle = background:#ccccff
| list1 =
{{Ionotropic glutamate receptor modulators}}
{{Monoamine reuptake inhibitors}}
{{Monoamine releasing agents}}
{{Nicotinic acetylcholine receptor modulators}}
{{Sigma receptor modulators}}
}}
{{Portal bar | Medicine | Viruses }}
{{Authority control}}


] ]
] ]
] ]
]
]
]
]
]
]
] ]
] ]
] ]
]

]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]
]