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			{{Short description|Medication used for high blood pressure and ADHD}}
	{{drugbox
			{{Distinguish|Guanine|Guanosine|Guanidine|Guaifenesin|Clonidine}}
	| verifiedrevid = 417979673
			{{Use dmy dates|date=January 2023}}
	| IUPAC_name = ''N''-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	| image = Guanfacine.svg
			{{Infobox drug
	| CASNo_Ref = {{cascite|correct|CAS}}
			| Verifiedfields = changed
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| verifiedrevid = 461124228
	| ChemSpiderID = 3399
			| image = Guanfacine.svg
	| UNII_Ref = {{fdacite|correct|FDA}}
			| width =
	| UNII = 30OMY4G3MK
			| alt =
	| InChI = 1/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15)
			| image2 = Guanfacine molecule ball.png
	| smiles = Clc1cccc(Cl)c1CC(=O)\N=C(/N)N
			| width2 =
	| InChIKey = INJOMKTZOLKMBF-UHFFFAOYAS
			| alt2 =
	| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 862
			<!-- Clinical data -->
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| tradename = Intuniv, others
	| StdInChI = 1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15)
			| Drugs.com = {{drugs.com|monograph|guanfacine}}
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| MedlinePlus = a601059
	| StdInChIKey = INJOMKTZOLKMBF-UHFFFAOYSA-N
			| DailyMedID = Guanfacine
	| CAS_number = 29110-47-2
			| routes_of_administration = ]
	| ATC_prefix = C02
			| class = ]
	| ATC_suffix = AC02
			| ATC_prefix = C02
	| ATC_supplemental =
			| ATC_suffix = AC02
	| PubChem = 3519
			| ATC_supplemental =
	| IUPHAR_ligand = 522
	| DrugBank = APRD00075
			<!-- Legal status -->
	| KEGG_Ref = {{keggcite|correct|kegg}}
			| legal_AU = S4
	| KEGG = D08031
			| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-chemical-entities-australia-2017 | access-date=9 April 2023}}</ref><ref>{{cite web | title=Prescription medicines and biologicals: TGA annual summary 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-and-biologicals-tga-annual-summary-2017 | access-date=31 March 2024}}</ref>
	| C=9 | H=9 | Cl=2 | N=3 | O=1
			| legal_CA = Rx-only
	| molecular_weight = 246.093 g/mol
			| legal_US = Rx-only
	| bioavailability = 99.9%
			| legal_US_comment = <ref name="Intuniv FDA label">{{Cite web |date=26 January 2021 |title=Intuniv- guanfacine tablet, extended release Intuniv- guanfacine kit |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528 |access-date=6 August 2022 |website=DailyMed |archive-date=6 August 2022 |archive-url=https://web.archive.org/web/20220806051328/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528 |url-status=live }}</ref><ref name="Tenex FDA label" />
	| protein_bound =
			| legal_EU = Rx-only
	| metabolism =
			| legal_EU_comment = <ref>{{cite web | title=Intuniv EPAR | website=European Medicines Agency | date=17 September 2015 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/intuniv | access-date=13 June 2024}}</ref>
	| elimination_half-life = 14.8–18.3 h
	| excretion = renal
			<!-- Pharmacokinetic data -->
	| pregnancy_category = B
			| bioavailability = 80–100% (IR), 58% (XR)<ref name="DM">{{Cite web |date=March 2007 |title=Guanfacine (guanfacine) Tablet |url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9fc0bdc2-5ba2-48dd-aa87-7b0050a2d6ce |access-date=9 November 2013 |website=DailyMed |publisher=Genpharm Inc. |archive-date=26 June 2022 |archive-url=https://web.archive.org/web/20220626115201/https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9fc0bdc2-5ba2-48dd-aa87-7b0050a2d6ce |url-status=live }}</ref><ref name="MSR">{{Cite web |title=guanfacine (Rx) - Intuniv, Tenex |url=http://reference.medscape.com/drug/intuniv-tenex-guanfacine-342384 |access-date=9 November 2013 |website=Medscape Reference |publisher=WebMD |archive-date=18 May 2019 |archive-url=https://web.archive.org/web/20190518174636/https://reference.medscape.com/drug/intuniv-tenex-guanfacine-342384 |url-status=live }}</ref>
	| legal_status = Rx-only
			| protein_bound = 70%<ref name = DM/><ref name = MSR/>
	| routes_of_administration = oral, ]
			| metabolism = ]<ref name = DM/><ref name = MSR/>
			| elimination_half-life = IR: 10–17 hours; XR: 17 hours (10–30) in adults & adolescents and 14 hours in children<ref name = DM/><ref name = MSR/><ref>{{Cite journal |vauthors=Hofer KN, Buck ML |year=2008 |title=New Treatment Options for Attention-Deficit/Hyperactivity Disorder (ADHD): Part II. Guanfacine |url=http://medscape.com/viewarticle/578747_4 |journal=Pediatric Pharmacotherapy |issue=14 |page=4 |access-date=30 July 2014 |archive-date=31 October 2015 |archive-url=https://web.archive.org/web/20151031172657/http://www.medscape.com/viewarticle/578747_4 |url-status=live }}</ref><ref>{{Cite journal |vauthors=Cruz MP |date=August 2010 |title=Guanfacine Extended-Release Tablets (Intuniv), a Nonstimulant Selective Alpha(2A)-Adrenergic Receptor Agonist For Attention-Deficit/Hyperactivity Disorder |journal=P & T |volume=35 |issue=8 |pages=448–451 |pmc=2935643 |pmid=20844694}}</ref>
			| excretion = Kidney (80%; 50% as unchanged drug)<ref name = DM/><ref name = MSR/>
			<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 29110-47-2
			| PubChem = 3519
			| IUPHAR_ligand = 522
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB01018
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 3399
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 30OMY4G3MK
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = D08031
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
			| ChEMBL = 862
			| synonyms =
			<!-- Chemical data -->
			| IUPAC_name = ''N''-(Diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
			| C = 9
			| H = 9
			| Cl = 2
			| N = 3
			| O = 1
			| SMILES = Clc1cccc(Cl)c1CC(=O)\N=C(/N)N
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChI = 1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15)
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = INJOMKTZOLKMBF-UHFFFAOYSA-N
	}}		}}
			<!-- Definition and medical uses -->
	'''Guanfacine''' (brand name '''Tenex''', and the extended release '''Intuniv''') is an ] of the ] subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α<sub>2A</sub> receptors in the prefrontal cortex.<ref name="Kolar">{{Citation |last=Kolar |first=Dusan |first2=Amanda |last2=Keller |first3=Maria |last3=Golfinopoulos |first4=Lucy |last4=Cumyn |first5=Cassidy |last5=Syer |first6=Lily |last6=Hechtman |lastauthoramp=yes |year=2008 |title=Treatment of adults with attention-deficit/hyperactivity disorder |journal=Neuropsychiatric Disease and Treatment |pmid=18728745 |volume=4 |issue=2 |pages=389–403 |pmc=2518387 }}.</ref> Guanfacine lowers both ] and ] ] by activating the ] α-2a norepinephrine autoreceptors, which results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone.<ref>{{Citation |last=Van Zwieten |first=P. |last2=Thoolen |first2=M. |lastauthoramp=yes |last3=Timmermans |first3=P. |year=1983 |title=The Pharmacology of Centrally Acting Antihypertensive Drugs |journal=British Journal of Clinical Pharmacology |volume=15 |issue=Suppl 4 |pages=455S–462S |pmc=1427667 }}.</ref> Its side-effects are dose dependent, with frequency and severity almost disappearing at doses of 2&nbsp;mg and less.<ref name="Jerie">{{Citation |last=Jerie |first=P. |year=1980 |title=Clinical Experience with Guanfacine in Long-Term Treatment of Hypertension: Adverse Reactions to Guanfacine |journal=British Journal of Clinical Pharmacology |volume=10 |pmid=6994770 |issue=Suppl 1 |pages=157S–164S |pmc=1430125 }}.</ref>
			'''Guanfacine''', sold under the brand name '''Tenex''' (]) and '''Intuniv''' (]) among others, is an ] ] medication used to treat ] (ADHD) and ].<ref name="Intuniv FDA label" /><ref name="AHFS2019">{{Cite web |title=Guanfacine Monograph for Professionals |url=https://www.drugs.com/monograph/guanfacine.html |archive-url=https://web.archive.org/web/20180115071707/https://www.drugs.com/monograph/guanfacine.html |archive-date=15 January 2018 |access-date=18 March 2019 |website=Drugs.com |publisher=American Society of Health-System Pharmacists }}</ref>
			<!-- Side effects and mechanism -->
			Common ]s include ], ], and ].<ref name=AHFS2019/> Other side effects may include ] and urinary problems.<ref name="BNF76">{{Cite book |title=British national formulary: BNF 76 |date=2018 |publisher=Pharmaceutical Press |isbn=978-0-85711-338-2 |edition=76 |pages=349–350}}</ref> It appears to work by activating ]s in the ], thereby decreasing ] activity.<ref name=AHFS2019/>
			<!-- Society and culture -->
			Guanfacine was first described by 1974<ref name="Turner1974" /> and was approved for medical use in the United States in 1986.<ref name=AHFS2019/> It is available as a ].<ref name=AHFS2019/> In 2022, it was the 275th most commonly prescribed medication in the United States, with more than 800,000 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 = Guanfacine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Guanfacine | access-date = 30 August 2024 }}</ref> Guanfacine is approved by the US FDA for monotherapy treatment of ADHD,<ref name="Intuniv FDA label" /> as well as being used for ] of ]s.<ref name="Intuniv FDA label" /><ref name="AHFS2019" /> Guanfacine is also used ] to treat ]s, ]s, and ] (PTSD).<ref name="b1">{{Cite book |vauthors=Boland RJ, Verduin ML, Sadock BJ |url=https://www.worldcat.org/oclc/1264172789 |title=Kaplan & Sadock's Concise Textbook of Clinical Psychiatry |year=2023 |isbn=978-1-9751-6748-6 |veditors=Ruiz P |edition=5th |location=Philadelphia | publisher = Wolters Kluwer |pages=1811–1812 |oclc=1264172789 |access-date=12 January 2023 |archive-date=8 February 2023 |archive-url=https://web.archive.org/web/20230208191429/https://www.worldcat.org/title/1264172789 |url-status=live }}</ref>
			==Medical uses==
			]
			Guanfacine (as brand name Intuniv) is ] for the treatment of attention deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive therapy to ]s.<ref name="Intuniv FDA label" /><ref name="Effects">{{Cite journal |vauthors=Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC |date=April 2013 |title=Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008 |journal=Psychiatric Services |volume=64 |issue=4 |pages=339–346 |doi=10.1176/appi.ps.201200147 |pmc=4023684 |pmid=23318985}}</ref> Guanfacine (as brand name Tenex) is indicated in the management of hypertension.<ref name="Tenex FDA label">{{cite web | title=Tenex- guanfacine hydrochloride tablet | website=DailyMed | date=8 May 2013 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=886e050c-dd22-4f35-ac3b-243f091125c3 | access-date=22 December 2024}}</ref>
			Unlike stimulant medications, guanfacine is regarded as having no ], and may even be used to reduce abuse of drugs including ] and ].<ref name="Walker2014">{{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 }}</ref> It is also FDA approved to treat ].<ref name="MSR" /> Guanfacine can offer a synergistic enhancement of stimulants such as ]s and ] for treating ADHD, and in many cases can also help control the ] profile of stimulant medications.<ref name=AHFS2019/><!-- Not considered a preferred agent for initial management of hypertension... stimulants (e.g., methylphenidate, amphetamines) remain the drugs of choice for the management of ADHD because of their greater efficacy compared with that of other drugs (e.g., guanfacine). However, guanfacine can be particularly helpful in patients where stimulants are contraindicated due to tics, substance abuse, or increased anxiety, e.g. guanfacine is particularly helpful in treating children who have been traumatized or abused.<ref name="pmid23683139">{{Cite journal |vauthors=Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A |date=May 2013 |title=An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents |journal=Journal of Child and Adolescent Psychopharmacology |volume=23 |issue=4 |pages=244–51 |doi=10.1089/cap.2012.0119 |pmc=3657282 |pmid=23683139}}</ref> The extended-release form of guanfacine is sold under the brand name, Intuniv, for children and adolescents who metabolize the drug more quickly than older adults and thus benefit from an extended-release preparation. Intuniv is also approved for adults with ADHD in Japan. --> For ADHD, it is claimed that guanfacine helps individuals better control behavior, inhibit inappropriate distractions and impulses, and inhibit inappropriate aggressive impulses.<ref name="ArnstenJin2012" /> ]s and ] have found guanfacine to be effective in the treatment of ADHD in both children and adults, with a moderate ] found in adults (] = -0.66).<ref name="pmid37166701">{{cite journal | vauthors = Radonjić NV, Bellato A, Khoury NM, Cortese S, Faraone SV | title = Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-analysis | journal = CNS Drugs | volume = 37 | issue = 5 | pages = 381–397 | date = May 2023 | pmid = 37166701 | doi = 10.1007/s40263-023-01005-8 | s2cid = 258616507 | url = }}</ref><ref name="pmid36944092">{{cite journal | vauthors = Yu S, Shen S, Tao M | title = Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis | journal = J Child Adolesc Psychopharmacol | volume = 33 | issue = 2 | pages = 40–50 | date = March 2023 | pmid = 36944092 | doi = 10.1089/cap.2022.0038 | s2cid = 257664282 | url = }}</ref><ref name="pmid28700715">{{cite journal | vauthors = Catalá-López F, Hutton B, Núñez-Beltrán A, Page MJ, Ridao M, Macías Saint-Gerons D, Catalá MA, Tabarés-Seisdedos R, Moher D | title = The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials | journal = PLOS ONE | volume = 12 | issue = 7 | pages = e0180355 | date = 2017 | pmid = 28700715 | pmc = 5507500 | doi = 10.1371/journal.pone.0180355 | doi-access = free | bibcode = 2017PLoSO..1280355C | url = }}</ref> A systematic review and meta-analysis also found that guanfacine reduced ] in children and adolescents with ADHD who also had or did not also have ], with a small-to-moderate effect size.<ref name="pmid25886655">{{cite journal | vauthors = Pringsheim T, Hirsch L, Gardner D, Gorman DA | title = The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 1: psychostimulants, alpha-2 agonists, and atomoxetine | journal = Can J Psychiatry | volume = 60 | issue = 2 | pages = 42–51 | date = February 2015 | pmid = 25886655 | pmc = 4344946 | doi = 10.1177/070674371506000202 | url = }}</ref> In any case, guanfacine and other α<sub>2</sub>-adrenergic receptor agonists are considered to be less effective than stimulants in the treatment of ADHD.<ref name="pmid25886655" /><ref name="pmid29460165">{{cite journal | vauthors = Padilha SC, Virtuoso S, Tonin FS, Borba HH, Pontarolo R | title = Efficacy and safety of drugs for attention deficit hyperactivity disorder in children and adolescents: a network meta-analysis | journal = Eur Child Adolesc Psychiatry | volume = 27 | issue = 10 | pages = 1335–1345 | date = October 2018 | pmid = 29460165 | doi = 10.1007/s00787-018-1125-0 | s2cid = 3402756 | url = }}</ref><ref name="pmid28700715" />
			Guanfacine is also used off-label to treat tic disorders, anxiety disorders such as generalized anxiety disorder, and PTSD.<ref>{{Cite journal |vauthors=Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL |date=September 2008 |title=Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring |journal=Child and Adolescent Psychiatry and Mental Health |volume=2 |issue=1 |pages=24 |doi=10.1186/1753-2000-2-24 |pmc=2566553 |pmid=18793403 |doi-access=free |title-link=doi}}</ref><ref name=b1/> Guanfacine and other ]s have ]-like action,<ref>{{cite journal | vauthors = Morrow BA, George TP, Roth RH | title = Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry | journal = Brain Research | volume = 1027 | issue = 1–2 | pages = 173–178 | date = November 2004 | pmid = 15494168 | doi = 10.1016/j.brainres.2004.08.057 | s2cid = 7066842 }}</ref> thereby reducing the emotional responses of the ], and strengthening ] regulation of emotion, action, and thought.<ref name="ReferenceA" /> These actions arise from both inhibition of ]-induced ] release, and from prominent, ] actions in the prefrontal cortex.<ref name="ReferenceA">{{cite journal | vauthors = Arnsten AF, Raskind MA, Taylor FB, Connor DF | title = The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder | journal = Neurobiology of Stress | volume = 1 | pages = 89–99 | date = January 2015 | pmid = 25436222 | pmc = 4244027 | doi = 10.1016/j.ynstr.2014.10.002 }}</ref> Due to its prolonged ], it also has been seen to improve sleep interrupted by ]s in PTSD patients.<ref>{{cite journal | vauthors = Kozaric-Kovacic D | title = Psychopharmacotherapy of posttraumatic stress disorder | journal = Croatian Medical Journal | volume = 49 | issue = 4 | pages = 459–475 | date = August 2008 | pmid = 18716993 | pmc = 2525822 | doi = 10.3325/cmj.2008.4.459 }}</ref> All of these actions likely contribute to the relief of the ], re-experiencing of ], and ] associated with PTSD.<ref>{{cite journal | vauthors = Kaminer D, Seedat S, Stein DJ | title = Post-traumatic stress disorder in children | journal = World Psychiatry | volume = 4 | issue = 2 | pages = 121–125 | date = June 2005 | pmid = 16633528 | pmc = 1414752 }}</ref> Guanfacine appears to be especially helpful in treating children who have been ] or ]d.<ref name="ReferenceA" />
			==Adverse effects==
			]s of guanfacine are ].<ref name="Jerie">{{Cite journal |vauthors=Jerie P |year=1980 |title=Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine |journal=British Journal of Clinical Pharmacology |volume=10 |issue=Suppl 1 |pages=157S–164S |doi=10.1111/j.1365-2125.1980.tb04924.x |pmc=1430125 |pmid=6994770}}</ref>
			Very common (>10% incidence) adverse effects include ], ], ], and ].<ref name="UKlabel2017">{{Cite web |date=June 2017 |title=Intuniv 1 mg, 2 mg, 3 mg, 4 mg prolonged-release tablets - Summary of Product Characteristics |url=https://www.medicines.org.uk/emc/medicine/31294 |publisher=UK Electronic Medicines Compendium |access-date=7 July 2017 |archive-date=15 January 2018 |archive-url=https://web.archive.org/web/20180115184531/https://www.medicines.org.uk/emc/medicine/31294 |url-status=dead }}</ref>
			Common (1–10% incidence) adverse effects include ], ], ], ], and ]es.<ref name=UKlabel2017/>
			Guanfacine has been reported to cause high rates of ] in children with ADHD, for instance 73% with guanfacine versus 6% with placebo in one trial.<ref name="pmid28391425" /><ref name="Rugino2018" />
			Guanfacine may worsen ] in children with ADHD, including reduced ].<ref name="pmid28391425" /><ref name="Rugino2018">{{cite journal | vauthors = Rugino TA | title = Effect on Primary Sleep Disorders When Children With ADHD Are Administered Guanfacine Extended Release | journal = J Atten Disord | volume = 22 | issue = 1 | pages = 14–24 | date = January 2018 | pmid = 25376194| doi = 10.1177/1087054714554932 | s2cid = 22675882 | url = }}</ref>
			A 2020 ] found side effects of guanfacine including ], ], and ].<ref name="pmid32394557">{{cite journal | vauthors = Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU | title = Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects | journal = World Psychiatry | volume = 19 | issue = 2 | pages = 214–232 | date = June 2020 | pmid = 32394557 | pmc = 7215080 | doi = 10.1002/wps.20765 | url = }}</ref>
			==Interactions==
			Guanfacine availability is significantly affected by the ] and ] ]s. Medications that ] or ] those enzymes change the amount of guanfacine in circulation and thus its efficacy and rate of adverse effects. Because of its impact on the ], it should be used with caution with other ] drugs. A similar concern is appropriate when it is used with ] medications.<ref name=UKlabel2017/>
			==Pharmacology==
			===Pharmacodynamics===
			{| class="wikitable floatright" style="font-size:small;"
			|+ Guanfacine<ref name="PDSP"/>
			|-
			! Site !! ''K''<sub>i</sub> (nM) !! Species !! Ref
			|-
			| ] || 50.3 – 93.3 || Human ||<ref name="Jasper">{{Cite journal |vauthors=Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM |date=April 1998 |title=Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated GTPgammaS binding |journal=Biochemical Pharmacology |volume=55 |issue=7 |pages=1035–1043 |doi=10.1016/s0006-2952(97)00631-x |pmid=9605427}}</ref><ref name="Porter">{{Cite journal |vauthors=Uhlén S, Porter AC, Neubig RR |date=December 1994 |title=The novel alpha-2 adrenergic radioligand -MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=271 |issue=3 |pages=1558–1565 |pmid=7996470}}</ref>
			|-
			| ] || 1,020 – 1,380 || Human ||<ref name="Jasper" /><ref name="Porter" />
			|-
			| ] || 1,120 – 3,890 || Human ||<ref name="Jasper" /><ref name="Porter" />
			|- class="sortbottom"
			| colspan="4" style="width: 1px;" | The smaller the value, the more strongly the drug binds to the site.
			|}
			Guanfacine is a highly ] ] of the ], with low ] for other ]s.<ref name=PDSP>{{Cite web |author-link=Bryan Roth |date=12 January 2011 |title=PDSP K<sub>i</sub> Database |url=http://pdsp.med.unc.edu/pdsp.php |url-status=dead |archive-url=https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php |archive-date=8 November 2013 |access-date=15 November 2013 |website=Psychoactive Drug Screening Program (PDSP) |publisher=University of North Carolina at Chapel Hill and the United States National Institute of Mental Health |vauthors=Roth BL, Driscol J}}</ref> However, it is also a ] ] agonist.<ref name="pmid37584406">{{cite journal | vauthors = Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD | title = 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery | journal = J Med Chem | volume = 66 | issue = 16 | pages = 11027–11039 | date = August 2023 | pmid = 37584406 | doi = 10.1021/acs.jmedchem.3c01178 | s2cid = 260924858 | url = | quote = These results strongly indicate substantial risks for treatments involving 5-HT2B agonists, and it has been recommended that all serotonergic drugs be screened for this functional profile.43,59 Additionally, there are cases of marketed drugs that were only later determined to have 5-HT2B activity. Of particular note is guanfacine, an FDA-approved medication for the treatment of attention deficit hyperactivity disorder (ADHD) that possesses potent 5-HT2B agonist activity in functional readouts to a similar degree as known valvulopathogens.66| pmc = 11073569 }}</ref><ref name="pmid21440001">{{cite journal | vauthors = Hutcheson JD, Setola V, Roth BL, Merryman WD | title = Serotonin receptors and heart valve disease--it was meant 2B | journal = Pharmacol Ther | volume = 132 | issue = 2 | pages = 146–57 | date = November 2011 | pmid = 21440001 | pmc = 3179857 | doi = 10.1016/j.pharmthera.2011.03.008 | url = }}</ref><ref name="AJMP">{{Cite journal |vauthors=Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, Revankar C, Robers M, Doucette C, Roth BL |date=October 2009 |title=Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment |journal=Molecular Pharmacology |volume=76 |issue=4 |pages=710–722 |doi=10.1124/mol.109.058057 |pmc=2769050 |pmid=19570945}}</ref><ref name="pmid24049061">{{cite journal | vauthors = Unett DJ, Gatlin J, Anthony TL, Buzard DJ, Chang S, Chen C, Chen X, Dang HT, Frazer J, Le MK, Sadeque AJ, Xing C, Gaidarov I | title = Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration | journal = J Pharmacol Exp Ther | volume = 347 | issue = 3 | pages = 645–59 | date = December 2013 | pmid = 24049061 | doi = 10.1124/jpet.113.207670 | s2cid = 8013309 | url = }}</ref>
			Guanfacine works by activating α<sub>2A</sub>-adrenoceptors<ref>{{Cite journal | vauthors = Tardner P |date=May 2023 |title=A Comprehensive Literature Review on Guanfacine as a Potential Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) |url=https://www.ijest.org/guanfacine-adhd-tardner-2023/ |journal=]}}</ref> within the ]. This leads to reduced ] ] outflow and thus a reduction in peripheral ], which lowers both ] and ] ].<ref name="VanZwieten">{{Cite journal |vauthors=van Zwieten PA, Timmermans PB |year=1983 |title=Centrally mediated hypotensive activity of B-HT 933 upon infusion via the cat's vertebral artery |journal=Pharmacology |volume=21 |issue=5 |pages=327–332 |doi=10.1111/j.1365-2125.1983.tb00311.x |pmc=1427667 |pmid=7433512}}</ref>
			In ADHD, guanfacine is thought to work by strengthening the regulation of attention and behavior by the ].<ref name="Arnsten">{{cite journal | vauthors = Arnsten AF | title = The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder | journal = Expert Review of Neurotherapeutics | volume = 10 | issue = 10 | pages = 1595–1605 | date = October 2010 | pmid = 20925474 | pmc = 3143019 | doi = 10.1586/ern.10.133 }}</ref><ref name="ArnstenJin2012" /> These enhancing effects on prefrontal cortical functions are believed to be due to drug stimulation of post-synaptic α<sub>2A</sub>-adrenoceptors on ], and are not dependent on activation of pre-synaptic α<sub>2A</sub>-adrenoceptors.<ref name="ArnstenJin2012" /> ] (cAMP)-mediated opening of ] and ] is inhibited, which enhances prefrontal cortical synaptic connectivity and ].<ref name="Arnsten" /><ref>{{Cite journal |vauthors=Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF |date=April 2007 |title=Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex |journal=Cell |volume=129 |issue=2 |pages=397–410 |doi=10.1016/j.cell.2007.03.015 |pmid=17448997 |doi-access=free |s2cid=741677}}</ref> In monkeys, guanfacine improves ], ] regulation, and ], and these actions are independent of its sedative effects.<ref name="ArnstenJin2012" /> The use of guanfacine for treating prefrontal disorders was developed by the Arnsten Lab at ].<ref name="Arnsten" /><ref name="ArnstenJin2012">{{Cite journal |vauthors=Arnsten AF, Jin LE |date=March 2012 |title=Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale |journal=The Yale Journal of Biology and Medicine |volume=85 |issue=1 |pages=45–58 |pmc=3313539 |pmid=22461743}}</ref>
			Guanfacine is much more selective for α<sub>2A</sub>-adrenergic receptors than ], which binds to and activates not only the α<sub>2A</sub>-adrenergic receptor but also ] and ]s and the ].<ref name="ArnstenJin2012" /> It is weaker than clonidine in producing ] and ], has weaker ] actions on the α<sub>2A</sub>-adrenergic receptor than clonidine (10-fold less effective in decreasing ] activity and ] ]), and may have greater efficacy in activating post-synaptic α<sub>2A</sub>-adrenergic receptors (as suggested by guanfacine being more potent than clonidine in enhancing prefrontal cortex-related ] in aged monkeys).<ref name="ArnstenJin2012" />
			Activation of the 5-HT<sub>2B</sub> receptor is a well-known ] and is associated with ].<ref name="pmid37584406" /><ref name="pmid21440001" /> However, not all 5-HT<sub>2B</sub> receptor agonists, for instance ], have this effect.<ref name="pmid37584406" /><ref name="pmid21440001" /> Guanfacine has not been associated with cardiac valvulopathy despite a long history of use, perhaps due to modest ] as a 5-HT<sub>2B</sub> receptor agonist.<ref name="pmid24049061" /><ref name="TGA2018">{{cite web | title = Australian Public Assessment Report for Guanfacine (as hydrochloride) | author = Therapeutic Goods Administration | url = https://www.tga.gov.au/sites/default/files/auspar-guanfacine-180503.pdf | date = May 2018}}</ref><ref name="Roihuvuo2022">Roihuvuo, E. (2022). Classical psychedelics and NBOMes as serotonin 2B receptor agonists: Valvulopathogenic signaling pathways and cardiac safety concerns (Master's thesis, Itä-Suomen yliopisto). http://urn.fi/urn:nbn:fi:uef-20220118</ref> In '']'' studies, guanfacine showed 100-fold lower ] for the 5-HT<sub>2B</sub> receptor than for the α<sub>2A</sub>-adrenergic receptor, 30-fold lower affinity for the 5-HT<sub>2B</sub> receptor than ], and 1,000-fold lower potency in activating the 5-HT<sub>2B</sub> receptor compared to serotonin.<ref name="TGA2018" /> It was concluded that at clinically relevant concentrations, guanfacine would not be expected to show significant binding to or activation of 5-HT<sub>2B</sub> receptors, and that it is unlikely that guanfacine is a cardiac valvulopathogen in humans.<ref name="TGA2018" /> In any case, different studies have reported different potencies of guanfacine as a 5-HT<sub>2B</sub> receptor agonist,<ref name="AJMP" /><ref name="pmid24049061" /><ref name="TGA2018" /><ref name="Roihuvuo2022" /> and as of 2018, no clinical data on the risk of cardiac valvulopathy with guanfacine were available.<ref name="pmid29315692">{{cite journal | vauthors = Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, Mladěnka A, Karlíčková J, Jahodář L, Vopršalová M, Varner KJ, Štěrba M | title = Comprehensive review of cardiovascular toxicity of drugs and related agents | journal = Med Res Rev | volume = 38 | issue = 4 | pages = 1332–1403 | date = July 2018 | pmid = 29315692 | pmc = 6033155 | doi = 10.1002/med.21476 | url = | quote = The list of valvulopathic drugs is short and can be seen in Table 7. According to a recent analysis, other drugs, in particular guanfacine, might possess some risk, but clinical data are yet not available.368–370}}</ref> As such, while the likelihood is thought to be low, guanfacine might still have a risk of cardiac valvulopathy.<ref name="TGA2018" />
			Guanfacine has been found to act as a full agonist of the ] (TAAR1) with an {{Abbrlink|EC<sub>50</sub>|half-maximal effective concentration}} and {{Abbrlink|E<sub>max</sub>|maximal efficacy}} of 20{{nbsp}}nM and ≥85% respectively.<ref>{{cite journal | pmc=10674299 | date=2023 | title=Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays | journal=Pharmaceuticals (Basel, Switzerland) | volume=16 | issue=11 | page=1632 | doi=10.3390/ph16111632 | doi-access=free | pmid=38004497 | vauthors = Cichero E, Francesconi V, Casini B, Casale M, Kanov E, Gerasimov AS, Sukhanov I, Savchenko A, Espinoza S, Gainetdinov RR, Tonelli M }}</ref><ref name="pmid38004497">{{cite journal | vauthors = Cichero E, Francesconi V, Casini B, Casale M, Kanov E, Gerasimov AS, Sukhanov I, Savchenko A, Espinoza S, Gainetdinov RR, Tonelli M | title = Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays | journal = Pharmaceuticals | volume = 16 | issue = 11 | date = November 2023 | page = 1632 | pmid = 38004497 | pmc = 10674299 | doi = 10.3390/ph16111632 | doi-access = free | url = }}</ref>
			===Pharmacokinetics===
			]
			Guanfacine has an ] ] of 80%. There is no clear evidence of any ]. Its ] is 17{{nbsp}}hours with the major ] route being ]. The principal ] is the 3-hydroxylated ], with evidence of moderate ], and the key intermediate is an ].<ref name="Kiechel">{{Cite journal |vauthors=Kiechel JR |year=1980 |title=Pharmacokinetics and metabolism of guanfacine in man: a review |journal=British Journal of Clinical Pharmacology |volume=10 |issue=Suppl 1 |pages=25S–32S |doi=10.1111/j.1365-2125.1980.tb04901.x |pmc=1430131 |pmid=6994775}}</ref> Elimination is not impacted by impaired ] function. As such, ] by the ] is the assumption for those with impaired renal function, as supported by the increased frequency of known side effects of ] and ].<ref>{{Cite journal |vauthors=Kirch W, Köhler H, Braun W |year=1980 |title=Elimination of guanfacine in patients with normal and impaired renal function |journal=British Journal of Clinical Pharmacology |volume=10 |issue=Suppl 1 |pages=33S–35S |doi=10.1111/j.1365-2125.1980.tb04902.x |pmc=1430110 |pmid=6994776}}</ref>
			{| class="wikitable sortable"
			|+Pharmacokinetic Data<ref>https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf</ref><ref>https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022037s018lbl.pdf</ref>
			!
			!Intuniv 1mg QD
			!Tenex 1mg QD
			!Unit
			|-
			|C<sub>max</sub>
			|1.0 ± 0.3
			|2.5 ± 0.6
			|ng/mL
			|-
			|AUC<sub>∞</sub>
			|32 ± 9
			|56 ± 15
			|ng*h/mL
			|-
			|T<sub>1/2</sub>
			|18 ± 4
			|16 ± 3
			|h (hours)
			|-
			|T<sub>max</sub>
			|6.0 (4.0 - 8.0)
			|3.0 (1.5 - 4.0)
			|h (hours)
			|-
			|Bioavailability
			|58%
			|80 - 100%
			|unitless
			|}
			==Preparation==
			Guanfacine can be prepared from equal parts {{chem name|methyl 2,6-dichlorophenylacetate}} and ]:<ref>{{Cite patent|number=US3632645A|title=Substituted phenylacetyl derivatives of guanidine o-alkylisoureas s-alkylisothioureas and p-nitrobenzylisothiourea|gdate=1972-01-04|invent1=Bream|invent2=Picard|inventor1-first=John Bernard|inventor2-first=Claude W.|url=https://patents.google.com/patent/US3632645A/en}}</ref>
			]
			==History==
			Guanfacine was first described in the literature by 1974.<ref name="Turner1974">Turner, A. S. (1974). BS 100-141 in the treatment of arterial hypertension. Seventh World Congr. of Cardiol., Abstr, 336.</ref><ref name="pmid4276642">{{cite journal | vauthors = Scholtysik G | title = Proceedings: Inhibition of effects of accelerator nerve stimulation in cats and rabbits by BS 100-141 and guanabenz | journal = Naunyn-Schmiedeberg's Arch Pharmacol | volume = 282 | issue = Suppl | pages = suppl 282:R86 | date = 1974 | pmid = 4276642 | doi = | url = }}</ref><ref name="pmid1243024">{{cite journal | vauthors = Bream JB, Lauener H, Picard CW, Scholtysik G, White TG | title = Substituted phenylacetylguanidines: a new class of antihypertensive agents | journal = Arzneimittelforschung | volume = 25 | issue = 10 | pages = 1477–82 | date = October 1975 | pmid = 1243024 | doi = | url = }}</ref><ref name="pmid241524">{{cite journal | vauthors = Saameli K, Scholtysik G, Waite R | title = Pharmacology of BS 100-141, a centrally acting antihypertensive drug | journal = Clinical and Experimental Pharmacology & Physiology | volume = 1975 | issue = Suppl 2 | pages = 207–212 | date = 1975 | pmid = 241524 | doi = }}</ref><ref name="pmid326262">{{cite journal | vauthors = Dubach UC, Huwyler R, Radielovic P, Singeisen M | title = A new centrally action antihypertensive agent guanfacine (BS 100-141) | journal = Arzneimittelforschung | volume = 27 | issue = 3 | pages = 674–6 | date = 1977 | pmid = 326262 | doi = | url = }}</ref> In 1986, guanfacine was approved by the FDA for the treatment of ] under the brand name Tenex.<ref name="Drugs@FDA-Tenex">{{cite web | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019032 | title=Drugs@FDA: FDA-Approved Drugs }}</ref> In 2010, guanfacine was approved by the FDA for the treatment of ] for people 6 to 17 years old.<ref name="Effects" /> It was approved for ADHD by the ] under the name Intuniv in 2015.<ref>{{Cite web |date=October 2015 |title=European Medicines Agency: Intuniv |url=http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F003759%2Fhuman_med_001910.jsp&mid=WC0b01ac058001d124 |publisher=Europa (web portal) |access-date=3 February 2016 |archive-date=16 August 2018 |archive-url=https://web.archive.org/web/20180816061628/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F003759%2Fhuman_med_001910.jsp&mid=WC0b01ac058001d124 |url-status=live }}</ref> It was added to the Australian ] for the treatment of ADHD in 2018.<ref>{{Cite news |title=New drugs listed on the PBS for rheumatoid arthritis, cystic fibrosis and ADHD |newspaper=Newsgp |url=https://www.racgp.org.au/newsGP/Clinical/New-drugs-listed-on-the-PBS-for-rheumatoid-arthrit |access-date=11 September 2018 |publisher=Royal Australian College of General Practitioners |archive-date=11 September 2018 |archive-url=https://web.archive.org/web/20180911114443/https://www.racgp.org.au/newsGP/Clinical/New-drugs-listed-on-the-PBS-for-rheumatoid-arthrit |url-status=live }}</ref>
			==Society and culture==
	==Uses==
			=== Legal status ===
	Guanfacine has the cardiovascular effect of lowering ].<ref name="Vitiello">{{Citation |last=Vitiello |first=B. |year=2008 |title=Understanding the Risk of Using Medications for ADHD with Respect to Physical Growth and Cardiovascular Function |journal=Child and Adolescent Psychiatric Clinics of North America |pmid=18295156 |volume=17 |issue=2 |pmc=2408826 |pages=459–xi |doi=10.1016/j.chc.2007.11.010 }}.</ref> It reduces ] not just in short-term, but also as shown in long-term studies with normalization of blood pressure of 54% treated over a year and 66% over two years.<ref>{{Citation |last=Jerie |first=P. |year=1980 |title=Clinical Experience with Guanfacine in Long-Term Treatment of Hypertension: Efficacy and Dosage |journal=British Journal of Clinical Pharmacology |pmid=6994777 |volume=10 |issue=Suppl 1 |pages=37S–47S |pmc=1430120 }}.</ref>
			In December 2024, the ] of the ] adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Paxneury, intended for the treatment of attention deficit hyperactivity disorder in children.<ref name="Paxneury EPAR" /> The applicant for this medicinal product is Neuraxpharm Pharmaceuticals S.L.<ref name="Paxneury EPAR" /> Paxneury is a generic of Intuniv, which has been authorized in the EU since September 2015.<ref name="Paxneury EPAR" /> It is also a hybrid medicine1 of Intuniv.<ref name="Paxneury EPAR" /> It contains the same active substance as Intuniv, but is available at higher strengths.<ref name="Paxneury EPAR">{{cite web | title=Paxneury EPAR | website=] (EMA) | date=12 December 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/paxneury | access-date=16 December 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref>
	]
	Guanfacine has also been approved by the FDA for the treatment of ] (ADHD) as an alternative to stimulant medications. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior <ref> Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010</ref>. Guanfacine is also used in conjunction with stimulants to augment therapeutic actions, counter side effects, reduce rebound, and when taken at night, to induce sleep.<ref>{{Citation |last=Zito |first=Julie M. |last2=Derivan |first2=Albert T. |last3=Kratochvil |first3=Christopher J. |last4=''et al.'' |year=2008 |first4=DJ |last5=Fegert |first5=JM |last6=Greenhill |first6=LL |title=Child and Adolescent Psychiatry and Mental Health |journal=Child and Adolescent Psychiatry and Mental Health |volume=2 |pmid=18793403 |issue=1 |pmc=2566553 |pages=24 |doi=10.1186/1753-2000-2-24 }}.</ref> Guanfacine is thought to improve regulation of behavior, attention and emotion through actions at post-synaptic, alpha-2A adrenergic receptors on prefrontal cortical neurons, which strengthen prefrontal cortical network connections <ref>Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF. Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 129:397-410, 2007</ref>.
	Another psychiatric use of guanfacine is for treatment of ] symptoms. Alpha-2A agonists such as guanfacine reduce sympathetic arousal, weaken the emotional responses of the amygdala, and strengthen prefrontal cortical regulation of emotion, action and thought. All of these actions likely contribute to the relief of the hyperarousal, re-experiencing, and impulsivity associated with PTSD.<ref>{{Citation |last=Kaminer |first=D. |last2=Seedat |first2=S. |lastauthoramp=yes |last3=Stein |first3=D. |year=2005 |title=Post-traumatic stress disorder in children |journal=World Psychiatry |pmid=16633528 |volume=4 |issue=2 |pages=121–125 |pmc=1414752 }}.</ref> Due to its prolonged half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients.<ref>{{Citation |last=Kozarlc-Kovaclc |first=D. |year=2008 |title=Psychopharmacotherapy of Posttraumatic Stress Disorder |journal=Croatian Medical Journal |pmid=18716993 |volume=49 |issue= 4 |pmc=2525822|pages=459–475 |doi=10.3325/cmj.2008.4.459 }}.</ref> However, a study showed no results for PTSD,<ref>{{Citation |title=No Improvement of Posttraumatic Stress Disorder Symptoms With Guanfacine Treatment |url=http://ajp.psychiatryonline.org/cgi/reprint/163/12/2186.pdf }}</ref> while ] did.<ref>{{Citation |title=Drug Helps PTSD Nightmares (prazosin) |url=http://www.research.va.gov/news/press_releases/ptsd-033007.cfm }}.</ref> According to recent studies (Srour ''et al.'', 2008) there is controversy as to guanfacine’s usefulness in treating tics. There has been success when tic symptoms are co-morbid with ADHD, and as such, guanfacine and other alpha-2-adrenergic agonists (]) are commonly the first choice for treatment. Guanfacine is also being investigated for treatment of withdrawal for opioids, alcohol, and nicotine.<ref>{{Citation |last=Sofuogul |first=M. |lastauthoramp=yes |last2=Sewell |first2=A. |year=2009 |title=Norepinephrine and Stimulant Addiction |journal=] |pmid=18811678 |volume=14 |issue=2 |pmc=2657197 |pages=119–129 |doi=10.1111/j.1369-1600.2008.00138.x }}.</ref>
	==Side effects==		===Brand names===
			Brand names include Tenex, Afken, Estulic, and Intuniv (an ] formulation).
	Usual: ], ], ], ], ], gas pains, ], ], ], and ] may occur.<ref>{{Cite web
	|url=http://healthlifeandstuff.com/2009/09/intuniv-for-adhd-concerns-efficacy/
	|title=Intuniv for ADHD: Efficacy, Side Effects
	|publisher=Health and Life
	}}</ref>
			==Research==
	Rare: ], ], ], ] of the hands or feet, ], yellowing of the eyes or skin.
			Guanfacine has been studied as a treatment for ] (PTSD). Evidence of efficacy in adults is limited, but one study found positive results in children with comorbid ADHD.<ref>{{Cite journal |vauthors=Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A |date=May 2013 |title=An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents |journal=Journal of Child and Adolescent Psychopharmacology |volume=23 |issue=4 |pages=244–251 |doi=10.1089/cap.2012.0119 |pmc=3657282 |pmid=23683139}}</ref> It may be also useful in adult PTSD patients who do not respond to ]s (SSRIs).<ref name="Belkin2015">{{Cite journal |vauthors=Belkin MR, Schwartz TL |year=2015 |title=Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder |journal=Drugs in Context |volume=4 |pages=212286 |doi=10.7573/dic.212286 |pmc=4544272 |pmid=26322115}}</ref>
			Results of studies using guanfacine to treat ] have been mixed.<ref>{{Cite journal |vauthors=Srour M, Lespérance P, Richer F, Chouinard S |date=August 2008 |title=Psychopharmacology of tic disorders |journal=Journal of the Canadian Academy of Child and Adolescent Psychiatry |volume=17 |issue=3 |pages=150–159 |pmc=2527768 |pmid=18769586}}</ref>
	Others: mental/mood changes, tingling of the hands or feet, ], ], ], vision changes, taste changes, ringing in the ears, ].
			Guanfacine does not appear to be effective for improving ] in children with ADHD and behavioral ].<ref name="pmid28391425">{{cite journal | vauthors = Anand S, Tong H, Besag FM, Chan EW, Cortese S, Wong IC | title = Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment | journal = Paediatr Drugs | volume = 19 | issue = 3 | pages = 235–250 | date = June 2017 | pmid = 28391425 | doi = 10.1007/s40272-017-0224-6 | s2cid = 2220464 | url = https://eprints.soton.ac.uk/412343/1/Anand.docx}}</ref> Instead, guanfacine worsened certain sleep parameters, for instance ], in one clinical trial.<ref name="pmid28391425" /><ref name="Rugino2018" />
	Cardiovascular side effects include orthostatic hypotension, dizziness, palpitations, and tachycardia upon standing, and possibly bradycardia. Rebound hypertension is a possibility with abrupt discontinuation, and as such a gradual discontinuation is recommended.<ref name=Vitiello/><ref>{{Citation |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 |month=April |pmid=18295156 |pmc=2408826 |doi=10.1016/j.chc.2007.11.010 |url=http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2408826&blobtype=pdf |format=PDF |postscript=.}}</ref>
			Guanfacine has been investigated for treatment of ] for ]s, ], and ].<ref>{{Cite journal |vauthors=Sofuoglu M, Sewell RA |date=April 2009 |title=Norepinephrine and stimulant addiction |journal=Addiction Biology |volume=14 |issue=2 |pages=119–129 |doi=10.1111/j.1369-1600.2008.00138.x |pmc=2657197 |pmid=18811678}}</ref> Guanfacine has been shown to help reduce stress-induced craving of nicotine in smokers trying to quit, which may involve strengthening of prefrontal cortex-mediated self-control.<ref>{{Cite journal |vauthors=McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten AF, Picciotto MR, Weinberger AH, Ashare R, Sinha R |date=March 2015 |title=A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation |journal=Journal of Psychopharmacology |volume=29 |issue=3 |pages=300–311 |doi=10.1177/0269881114562091 |pmc=4376109 |pmid=25516371}}</ref>
	==Psychological indications==
	In animal models, guanfacine is seen to affect a number of cognitive factors, including working memory improvement, distractibility reduction, response inhibition improvement, and attention control<ref>Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010</ref>. Performance increases in spatial working memory have also been observed in humans<ref>Jäkälä P, Riekkinen M, Sirviö J, Koivisto E, Kejonen K, Vanhanen M, Riekkinen P Jr. Guanfacine, but not clonidine, improves planning and working memory performance in humans. Neuropsychopharmacology. 20:460-70, 1999.</ref>.
			Guanfacine has been researched for treatment of a variety of conditions impacting ] function, including cognitive and attentional problems in people with ], ], ]s, and the ].<ref name="ArnstenJin2012" /><ref name="pmid33075480">{{cite journal | vauthors = Arnsten AF | title = Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species | journal = Neurobiol Learn Mem | volume = 176 | issue = | pages = 107327 | date = December 2020 | pmid = 33075480 | pmc = 7567669 | doi = 10.1016/j.nlm.2020.107327 | url = }}</ref>
	==Pharmacokinetics and metabolism==
	Guanfacine shows an absolute bioavailability of nearly 100%. There is no clear evidence of any first-pass metabolism. Elimination half-life is 17 hours with the major elimination route being renal. The principal metabolite is the 3-hydroxy derivative, with evidence of moderate biotransformation, and the key intermediate being an epoxide.<ref name="Kiechel">{{Citation |last=Kiechel |first=J. |year=1980 |title=Pharmacokinetics and Metabolism of Guanfacine in Man: A Review |journal=British Journal of Clinical Pharmacology |pmid=6994775 |volume=10 |issue=Suppl 1 |pages=25S–32S |pmc=1430131 }}.</ref> It is also shown that elimination in patients with impaired renal function does not differ significantly from those with normal renal function. As such, metabolism by liver is the assumption for those with impaired renal function, as supported by increased frequency of known side effects of orthostatic hypotension and sedation.<ref>{{Citation |last=Kirch |first=W. |last2=Kohler |first2=H. |lastauthoramp=yes |last3=Braun |first3=W. |year=1980 |title=Elimination of Guanfacine in Patients with Normal and Impaired Renal Function |journal=British Journal of Clinical Pharmacology |pmid=6994776 |volume=10 |issue=Suppl 1 |pages=33S–35S |pmc=1430110 }}.</ref> Guanfacine’s enhancing effects on the working-memory functions of the pre-frontal cortex is due to inhibition of cAMP-mediated signaling, which is effected by the Gi proteins that are generally coupled to the post-synaptic alpha-2a-adrenoceptors that guanfacine stimulates through binding.<ref>{{Citation |last=Ramos |first=Brian P. |last2=Stark |first2=David |last3=Verduzco |first3=Luis |last4=van Dyck |first4=Christopher H. |last5=Arnsten |first5=Amy F. T. |year=2006 |title=α2A-stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals |journal=Learning & Memory |pmid=17101879 |volume=13 |issue=6 |pmc=1783631 |pages=770–776 |doi=10.1101/lm.298006 }}.</ref>
			Guanfacine is being studied for the possible treatment of ].<ref name="pmid37368329">{{cite journal | vauthors = Fesharaki Zadeh A, Arnsten AF, Wang M | title = Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID | journal = Neurol Int | volume = 15 | issue = 2 | pages = 725–742 | date = May 2023 | pmid = 37368329 | pmc = 10303664 | doi = 10.3390/neurolint15020045 | doi-access = free | url = }}</ref><ref name="pmid37029295">{{cite journal | vauthors = Arnsten AF, Ishizawa Y, Xie Z | title = Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders | journal = Mol Psychiatry | volume = 28| issue = 11| pages = 4540–4552 | date = April 2023 | pmid = 37029295 | pmc = 10080530 | doi = 10.1038/s41380-023-02057-4 | url = }}</ref><ref name="Fesharaki-ZadehLoweArnsten2023">{{cite journal | vauthors = Reiken S, Sittenfeld L, Dridi H, Liu Y, Liu X, Marks AR | title = Alzheimer's-like signaling in brains of COVID-19 patients | journal = Alzheimer's & Dementia | volume = 18 | issue = 5 | pages = 955–965 | date = May 2022 | pmc = 9691274 | doi = 10.1016/j.nerep.2022.100154 }}</ref>
	==Notes and references==
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	==External links==		==References==
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