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Clinical data
Trade namesEstulic, Intuniv, Tenex, others
License data
Routes of
By mouth
Drug classCentrally acting α2A- adrenergic receptor agonist
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80–100% (IR), 58% (XR)[4][5]
Protein binding70%[4][5]
Elimination half-lifeIR: 10–17 hours; XR: 17 hours (10–30) in adults & adolescents and 14 hours in children[4][5][6][7]
ExcretionKidney (80%; 50% [range: 40–75%] as unchanged drug)[4][5]
  • N-(Diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.044.933 Edit this at Wikidata
Chemical and physical data
Molar mass246.09 g·mol−1
3D model (JSmol)
  • Clc1cccc(Cl)c1CC(=O)\N=C(/N)N
  • InChI=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) checkY
 ☒NcheckY (what is this?)  (verify)

Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure.[3][8] Guanfacine is FDA-approved for monotherapy treatment of ADHD,[3] as well as being used for augmentation of other treatments, such as stimulants.[8] Guanfacine is also used off-label to treat tic disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).[9]

Common side effects include sleepiness, constipation, and dry mouth.[8] Other side effects may include low blood pressure and urinary problems.[10] The FDA has categorized Guanfacine as "Category B" in pregnancy, which means animal-reproduction studies have not demonstrated a fetal risk or an adverse effect during pregnancy or breastfeeding.[11][10] It appears to work by activating α2A-adrenergic receptors in the brain, thereby decreasing sympathetic nervous system activity.[8]

Guanfacine was first described by 1974[12] and was approved for medical use in the United States in 1986.[8] It is available as a generic medication.[8] In 2021, it was the 231st most commonly prescribed medication in the United States, with more than 1 million prescriptions.[13][14]

Medical uses[edit]

Red pills
1 mg guanfacine tablets.

Guanfacine is FDA-approved as monotherapy or augmentation with stimulants to treat attention deficit hyperactivity disorder (ADHD).[3][15][16] Unlike stimulant medications, guanfacine is regarded as having no abuse potential, and may even be used to reduce abuse of drugs including nicotine and cocaine.[17] It is also FDA approved to treat high blood pressure.[5] Guanfacine can offer a synergistic enhancement of stimulants such as amphetamines and methylphenidate for treating ADHD, and in many cases can also help control the side effect profile of stimulant medications.[8] For ADHD, it is claimed that guanfacine helps individuals better control behavior, inhibit inappropriate distractions and impulses, and inhibit inappropriate aggressive impulses.[18] Systematic reviews and meta-analyses have found guanfacine to be effective in the treatment of ADHD in both children and adults, with a moderate effect size found in adults (Hedges' g = -0.66).[19][20][21] A systematic review and meta-analysis also found that guanfacine reduced oppositional behavior in children and adolescents with ADHD who also had or did not also have oppositional defiant disorder, with a small-to-moderate effect size.[22] In any case, guanfacine and other α2-adrenergic receptor agonists are considered to be less effective than stimulants in the treatment of ADHD.[22][23][21]

Guanfacine is also used off-label to treat tic disorders, anxiety disorders such as generalized anxiety disorder, and PTSD.[9] Guanfacine and other α2A-adrenergic receptor agonists have anxiolytic-like action,[24] thereby reducing the emotional responses of the amygdala, and strengthening prefrontal cortical regulation of emotion, action, and thought.[25] These actions arise from both inhibition of stress-induced catecholamine release, and from prominent, post-synaptic actions in the prefrontal cortex.[25] Due to its prolonged elimination half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients.[26] All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD.[27] Guanfacine appears to be especially helpful in treating children who have been traumatized or abused.[25]

Adverse effects[edit]

Side effects of guanfacine are dose-dependent.[28]

Very common (>10% incidence) adverse effects include sleepiness, tiredness, headache, and stomach ache.[29]

Common (1–10% incidence) adverse effects include decreased appetite, nausea, dry mouth, urinary incontinence, and rashes.[29]

Guanfacine has been reported to cause high rates of somnolence in children with ADHD, for instance 73% with guanfacine versus 6% with placebo in one trial.[30][31]

Guanfacine may worsen sleep in children with ADHD, including reduced total sleep time.[30][31]

A 2020 systematic review found side effects of guanfacine including abdominal pain, sedation, and QT prolongation.[32]


Guanfacine availability is significantly affected by the CYP3A4 and CYP3A5 enzymes. Medications that inhibit or induce those enzymes change the amount of guanfacine in circulation and thus its efficacy and rate of adverse effects. Because of its impact on the heart, it should be used with caution with other cardioactive drugs. A similar concern is appropriate when it is used with sedating medications.[29]



Site Ki (nM) Species Ref
α2A 50.3 – 93.3 Human [34][35]
α2B 1,020 – 1,380 Human [34][35]
α2C 1,120 – 3,890 Human [34][35]
The smaller the value, the more strongly the drug binds to the site.

Guanfacine is a highly selective agonist of the α2A-adrenergic receptor, with low affinity for other receptors.[33] However, it is also a 5-HT2B receptor agonist.[36][37][38][39]

Guanfacine works by activating α2A-adrenoceptors[40] within the central nervous system. This leads to reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone, which lowers both systolic and diastolic blood pressure.[41]

In ADHD, guanfacine is thought to work by strengthening the regulation of attention and behavior by the prefrontal cortex.[42][18] These enhancing effects on prefrontal cortical functions are believed to be due to drug stimulation of post-synaptic α2A-adrenoceptors on dendritic spines, and are not dependent on activation of pre-synaptic α2A-adrenoceptors.[18] Cyclic adenosine monophosphate (cAMP)-mediated opening of HCN and KCNQ channels is inhibited, which enhances prefrontal cortical synaptic connectivity and neuronal firing.[42][43] In monkeys, guanfacine improves working memory, attention regulation, and behavioral inhibition, and these actions are independent of its sedative effects.[18] The use of guanfacine for treating prefrontal disorders was developed by the Arnsten Lab at Yale University.[42][18]

Guanfacine is much more selective for α2A-adrenergic receptors than clonidine, which binds to and activates not only the α2A-adrenergic receptor but also α2B- and α2C-adrenergic receptors and the imidazoline receptor.[18] It is weaker than clonidine in producing hypotension and sedation, has weaker pre-synaptic actions on the α2A-adrenergic receptor than clonidine (10-fold less effective in decreasing locus coeruleus activity and norepinephrine release), and may have greater efficacy in activating post-synaptic α2A-adrenergic receptors (as suggested by guanfacine being more potent than clonidine in enhancing prefrontal cortex-related working memory in aged monkeys).[18]

Activation of the 5-HT2B receptor is a well-known antitarget and is associated with cardiac valvulopathy.[36][37] However, not all 5-HT2B receptor agonists, for instance ropinirole, have this effect.[36][37] Guanfacine has not been associated with cardiac valvulopathy despite a long history of use, perhaps due to modest potency as a 5-HT2B receptor agonist.[39][44][45] In in vitro studies, guanfacine showed 100-fold lower affinity for the 5-HT2B receptor than for the α2A-adrenergic receptor, 30-fold lower affinity for the 5-HT2B receptor than serotonin, and 1,000-fold lower potency in activating the 5-HT2B receptor compared to serotonin.[44] It was concluded that at clinically relevant concentrations, guanfacine would not be expected to show significant binding to or activation of 5-HT2B receptors, and that it is unlikely that guanfacine is a cardiac valvulopathogen in humans.[44] In any case, different studies have reported different potencies of guanfacine as a 5-HT2B receptor agonist,[38][39][44][45] and as of 2018, no clinical data on the risk of cardiac valvulopathy with guanfacine were available.[46] As such, while the likelihood is thought to be low, guanfacine might still have a risk of cardiac valvulopathy.[44]


Guanfacine has an oral bioavailability of 80%. There is no clear evidence of any first-pass metabolism. Its elimination half-life is 17 hours with the major elimination route being renal. The principal metabolite is the 3-hydroxylated derivative, with evidence of moderate biotransformation, and the key intermediate is an epoxide.[47] Elimination is not impacted by impaired renal function. As such, metabolism by the liver is the assumption for those with impaired renal function, as supported by the increased frequency of known side effects of orthostatic hypotension and sedation.[48]


Guanfacine can be prepared from equal parts methyl 2,6-dichlorophenylacetate and guanidine:[49]


Guanfacine was first described in the literature by 1974.[12][50][51][52][53] In 1986, guanfacine was approved by the FDA for the treatment of hypertension under the brand name Tenex.[54] In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6 to 17 years old.[15] It was approved for ADHD by the European Medicines Agency under the name Intuniv in 2015.[55] It was added to the Australian Pharmaceutical Benefits Scheme for the treatment of ADHD in 2018.[56]

Society and culture[edit]

Brand names[edit]

Brand names include Tenex, Afken, Estulic, and Intuniv (an extended release formulation).


Guanfacine has been studied as a treatment for post-traumatic stress disorder (PTSD). Evidence of efficacy in adults is limited, but one study found positive results in children with comorbid ADHD.[57] It may be also useful in adult PTSD patients who do not respond to selective serotonin reuptake inhibitors (SSRIs).[58]

Results of studies using guanfacine to treat Tourette's syndrome have been mixed.[59]

Guanfacine does not appear to be effective for improving sleep in children with ADHD and behavioral insomnia.[30] Instead, guanfacine worsened certain sleep parameters, for instance total sleep time, in one clinical trial.[30][31]

Guanfacine has been investigated for treatment of withdrawal for opioids, ethanol, and nicotine.[60] 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.[61]

Guanfacine has been researched for treatment of a variety of conditions impacting prefrontal cortex function, including cognitive and attentional problems in people with traumatic brain injury, stroke, schizophreniform disorders, and the elderly.[18][62]

Guanfacine is being studied for the possible treatment of long COVID.[63][64][65]


  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
  2. ^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.
  3. ^ a b c d "Intuniv- guanfacine tablet, extended release Intuniv- guanfacine kit". DailyMed. 26 January 2021. Archived from the original on 6 August 2022. Retrieved 6 August 2022.
  4. ^ a b c d e "Guanfacine (guanfacine) Tablet [Genpharm Inc.]". DailyMed. Genpharm Inc. March 2007. Archived from the original on 26 June 2022. Retrieved 9 November 2013.
  5. ^ a b c d e f "guanfacine (Rx) - Intuniv, Tenex". Medscape Reference. WebMD. Archived from the original on 18 May 2019. Retrieved 9 November 2013.
  6. ^ Hofer KN, Buck ML (2008). "New Treatment Options for Attention-Deficit/Hyperactivity Disorder (ADHD): Part II. Guanfacine". Pediatric Pharmacotherapy (14): 4. Archived from the original on 31 October 2015. Retrieved 30 July 2014.
  7. ^ Cruz MP (August 2010). "Guanfacine Extended-Release Tablets (Intuniv), a Nonstimulant Selective Alpha(2A)-Adrenergic Receptor Agonist For Attention-Deficit/Hyperactivity Disorder". P & T. 35 (8): 448–451. PMC 2935643. PMID 20844694.
  8. ^ a b c d e f g "Guanfacine Monograph for Professionals". American Society of Health-System Pharmacists. Archived from the original on 15 January 2018. Retrieved 18 March 2019.
  9. ^ a b Boland RJ, Verduin ML, Sadock BJ (2023). Ruiz P (ed.). Kaplan & Sadock's Concise Textbook of Clinical Psychiatry (5th ed.). Philadelphia. pp. 1811–1812. ISBN 978-1-9751-6748-6. OCLC 1264172789. Archived from the original on 8 February 2023. Retrieved 12 January 2023.{{cite book}}: CS1 maint: location missing publisher (link)
  10. ^ a b British national formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 349–350. ISBN 978-0-85711-338-2.
  11. ^ "Patient Information. INTUNIV (in-TOO-niv) (guanfacine). Extended-Release Tablets" (PDF). Archived (PDF) from the original on 13 October 2022. Retrieved 12 October 2022.
  12. ^ a b Turner, A. S. (1974). BS 100-141 in the treatment of arterial hypertension. Seventh World Congr. of Cardiol., Abstr, 336.
  13. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  14. ^ "Guanfacine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  15. ^ a b Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, et al. (April 2013). "Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008". Psychiatric Services. 64 (4): 339–346. doi:10.1176/ PMC 4023684. PMID 23318985.
  16. ^ Zito JM, Derivan AT, Kratochvil CJ, Safer DJ, Fegert JM, Greenhill LL (September 2008). "Off-label psychopharmacologic prescribing for children: history supports close clinical monitoring". Child and Adolescent Psychiatry and Mental Health. 2 (1): 24. doi:10.1186/1753-2000-2-24. PMC 2566553. PMID 18793403.
  17. ^ Clemow DB, Walker DJ (September 2014). "The potential for misuse and abuse of medications in ADHD: a review". Postgraduate Medicine. 126 (5): 64–81. doi:10.3810/pgm.2014.09.2801. PMID 25295651. S2CID 207580823.
  18. ^ a b c d e f g h Arnsten AF, Jin LE (March 2012). "Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale". The Yale Journal of Biology and Medicine. 85 (1): 45–58. PMC 3313539. PMID 22461743.
  19. ^ Radonjić NV, Bellato A, Khoury NM, Cortese S, Faraone SV (May 2023). "Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-analysis". CNS Drugs. 37 (5): 381–397. doi:10.1007/s40263-023-01005-8. PMID 37166701. S2CID 258616507.
  20. ^ Yu S, Shen S, Tao M (March 2023). "Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis". J Child Adolesc Psychopharmacol. 33 (2): 40–50. doi:10.1089/cap.2022.0038. PMID 36944092. S2CID 257664282.
  21. ^ a b Catalá-López F, Hutton B, Núñez-Beltrán A, Page MJ, Ridao M, Macías Saint-Gerons D, et al. (2017). "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". PLOS ONE. 12 (7): e0180355. Bibcode:2017PLoSO..1280355C. doi:10.1371/journal.pone.0180355. PMC 5507500. PMID 28700715.
  22. ^ a b Pringsheim T, Hirsch L, Gardner D, Gorman DA (February 2015). "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". Can J Psychiatry. 60 (2): 42–51. doi:10.1177/070674371506000202. PMC 4344946. PMID 25886655.
  23. ^ Padilha SC, Virtuoso S, Tonin FS, Borba HH, Pontarolo R (October 2018). "Efficacy and safety of drugs for attention deficit hyperactivity disorder in children and adolescents: a network meta-analysis". Eur Child Adolesc Psychiatry. 27 (10): 1335–1345. doi:10.1007/s00787-018-1125-0. PMID 29460165. S2CID 3402756.
  24. ^ Morrow BA, George TP, Roth RH (November 2004). "Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry". Brain Research. 1027 (1–2): 173–178. doi:10.1016/j.brainres.2004.08.057. PMID 15494168. S2CID 7066842.
  25. ^ a b c Arnsten AF, Raskind MA, Taylor FB, Connor DF (January 2015). "The Effects of Stress Exposure on Prefrontal Cortex: Translating Basic Research into Successful Treatments for Post-Traumatic Stress Disorder". Neurobiology of Stress. 1: 89–99. doi:10.1016/j.ynstr.2014.10.002. PMC 4244027. PMID 25436222.
  26. ^ Kozaric-Kovacic D (August 2008). "Psychopharmacotherapy of posttraumatic stress disorder". Croatian Medical Journal. 49 (4): 459–475. doi:10.3325/cmj.2008.4.459. PMC 2525822. PMID 18716993.
  27. ^ Kaminer D, Seedat S, Stein DJ (June 2005). "Post-traumatic stress disorder in children". World Psychiatry. 4 (2): 121–125. PMC 1414752. PMID 16633528.
  28. ^ Jerie P (1980). "Clinical experience with guanfacine in long-term treatment of hypertension. Part II: adverse reactions to guanfacine". British Journal of Clinical Pharmacology. 10 (Suppl 1): 157S–164S. doi:10.1111/j.1365-2125.1980.tb04924.x. PMC 1430125. PMID 6994770.
  29. ^ a b c "Intuniv 1 mg, 2 mg, 3 mg, 4 mg prolonged-release tablets - Summary of Product Characteristics". UK Electronic Medicines Compendium. June 2017. Archived from the original on 15 January 2018. Retrieved 7 July 2017.
  30. ^ a b c d Anand S, Tong H, Besag FM, Chan EW, Cortese S, Wong IC (June 2017). "Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment". Paediatr Drugs. 19 (3): 235–250. doi:10.1007/s40272-017-0224-6. PMID 28391425. S2CID 2220464.
  31. ^ a b c Rugino TA (January 2018). "Effect on Primary Sleep Disorders When Children With ADHD Are Administered Guanfacine Extended Release". J Atten Disord. 22 (1): 14–24. doi:10.1177/1087054714554932. PMID 25376194. S2CID 22675882.
  32. ^ Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, et al. (June 2020). "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". World Psychiatry. 19 (2): 214–232. doi:10.1002/wps.20765. PMC 7215080. PMID 32394557.
  33. ^ a b Roth BL, Driscol J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 15 November 2013.
  34. ^ a b c Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, et al. (April 1998). "Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding". Biochemical Pharmacology. 55 (7): 1035–1043. doi:10.1016/s0006-2952(97)00631-x. PMID 9605427.
  35. ^ a b c Uhlén S, Porter AC, Neubig RR (December 1994). "The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors". The Journal of Pharmacology and Experimental Therapeutics. 271 (3): 1558–1565. PMID 7996470.
  36. ^ a b c Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD (August 2023). "2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery". J Med Chem. 66 (16): 11027–11039. doi:10.1021/acs.jmedchem.3c01178. PMID 37584406. S2CID 260924858. 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
  37. ^ a b c Hutcheson JD, Setola V, Roth BL, Merryman WD (November 2011). "Serotonin receptors and heart valve disease--it was meant 2B". Pharmacol Ther. 132 (2): 146–57. doi:10.1016/j.pharmthera.2011.03.008. PMC 3179857. PMID 21440001.
  38. ^ a b Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, et al. (October 2009). "Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment". Molecular Pharmacology. 76 (4): 710–722. doi:10.1124/mol.109.058057. PMC 2769050. PMID 19570945.
  39. ^ a b c Unett DJ, Gatlin J, Anthony TL, Buzard DJ, Chang S, Chen C, et al. (December 2013). "Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration". J Pharmacol Exp Ther. 347 (3): 645–59. doi:10.1124/jpet.113.207670. PMID 24049061. S2CID 8013309.
  40. ^ Tardner P (May 2023). "A Comprehensive Literature Review on Guanfacine as a Potential Treatment for Attention-Deficit/Hyperactivity Disorder (ADHD)". International Journal of Environmental Science and Technology.
  41. ^ van Zwieten PA, Timmermans PB (1983). "Centrally mediated hypotensive activity of B-HT 933 upon infusion via the cat's vertebral artery". Pharmacology. 21 (5): 327–332. doi:10.1111/j.1365-2125.1983.tb00311.x. PMC 1427667. PMID 7433512.
  42. ^ a b c Arnsten AF (October 2010). "The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder". Expert Review of Neurotherapeutics. 10 (10): 1595–1605. doi:10.1586/ern.10.133. PMC 3143019. PMID 20925474.
  43. ^ Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, et al. (April 2007). "Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex". Cell. 129 (2): 397–410. doi:10.1016/j.cell.2007.03.015. PMID 17448997. S2CID 741677.
  44. ^ a b c d e Therapeutic Goods Administration (May 2018). "Australian Public Assessment Report for Guanfacine (as hydrochloride)" (PDF).
  45. ^ a b 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).
  46. ^ Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, et al. (July 2018). "Comprehensive review of cardiovascular toxicity of drugs and related agents". Med Res Rev. 38 (4): 1332–1403. doi:10.1002/med.21476. PMC 6033155. PMID 29315692. 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
  47. ^ Kiechel JR (1980). "Pharmacokinetics and metabolism of guanfacine in man: a review". British Journal of Clinical Pharmacology. 10 (Suppl 1): 25S–32S. doi:10.1111/j.1365-2125.1980.tb04901.x. PMC 1430131. PMID 6994775.
  48. ^ Kirch W, Köhler H, Braun W (1980). "Elimination of guanfacine in patients with normal and impaired renal function". British Journal of Clinical Pharmacology. 10 (Suppl 1): 33S–35S. doi:10.1111/j.1365-2125.1980.tb04902.x. PMC 1430110. PMID 6994776.
  49. ^ US3632645A, Bream, John Bernard & Picard, Claude W., "Substituted phenylacetyl derivatives of guanidine o-alkylisoureas s-alkylisothioureas and p-nitrobenzylisothiourea", issued 1972-01-04 
  50. ^ Scholtysik G (1974). "Proceedings: Inhibition of effects of accelerator nerve stimulation in cats and rabbits by BS 100-141 and guanabenz". Naunyn-Schmiedeberg's Arch Pharmacol. 282 (Suppl): suppl 282:R86. PMID 4276642.
  51. ^ Bream JB, Lauener H, Picard CW, Scholtysik G, White TG (October 1975). "Substituted phenylacetylguanidines: a new class of antihypertensive agents". Arzneimittelforschung. 25 (10): 1477–82. PMID 1243024.
  52. ^ Saameli K, Scholtysik G, Waite R (1975). "Pharmacology of BS 100-141, a centrally acting antihypertensive drug". Clin Exp Pharmacol Physiol. Suppl 2: 207–12. PMID 241524.
  53. ^ Dubach UC, Huwyler R, Radielovic P, Singeisen M (1977). "A new centrally action antihypertensive agent guanfacine (BS 100-141)". Arzneimittelforschung. 27 (3): 674–6. PMID 326262.
  54. ^ "Drugs@FDA: FDA-Approved Drugs".
  55. ^ "European Medicines Agency: Intuniv". Europa (web portal). October 2015. Archived from the original on 16 August 2018. Retrieved 3 February 2016.
  56. ^ "New drugs listed on the PBS for rheumatoid arthritis, cystic fibrosis and ADHD". Royal Australian College of General Practitioners. Archived from the original on 11 September 2018. Retrieved 11 September 2018.
  57. ^ Connor DF, Grasso DJ, Slivinsky MD, Pearson GS, Banga A (May 2013). "An open-label study of guanfacine extended release for traumatic stress related symptoms in children and adolescents". Journal of Child and Adolescent Psychopharmacology. 23 (4): 244–251. doi:10.1089/cap.2012.0119. PMC 3657282. PMID 23683139.
  58. ^ Belkin MR, Schwartz TL (2015). "Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder". Drugs in Context. 4: 212286. doi:10.7573/dic.212286. PMC 4544272. PMID 26322115.
  59. ^ Srour M, Lespérance P, Richer F, Chouinard S (August 2008). "Psychopharmacology of tic disorders". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 17 (3): 150–159. PMC 2527768. PMID 18769586.
  60. ^ Sofuoglu M, Sewell RA (April 2009). "Norepinephrine and stimulant addiction". Addiction Biology. 14 (2): 119–129. doi:10.1111/j.1369-1600.2008.00138.x. PMC 2657197. PMID 18811678.
  61. ^ McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten AF, Picciotto MR, et al. (March 2015). "A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation". Journal of Psychopharmacology. 29 (3): 300–311. doi:10.1177/0269881114562091. PMC 4376109. PMID 25516371.
  62. ^ Arnsten AF (December 2020). "Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species". Neurobiol Learn Mem. 176: 107327. doi:10.1016/j.nlm.2020.107327. PMC 7567669. PMID 33075480.
  63. ^ Fesharaki Zadeh A, Arnsten AF, Wang M (May 2023). "Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID". Neurol Int. 15 (2): 725–742. doi:10.3390/neurolint15020045. PMC 10303664. PMID 37368329.
  64. ^ Arnsten AF, Ishizawa Y, Xie Z (April 2023). "Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders". Mol Psychiatry. 28 (11): 4540–4552. doi:10.1038/s41380-023-02057-4. PMC 10080530. PMID 37029295.
  65. ^ Fesharaki-Zadeh A, Lowe N, Arnsten AF (2023). "Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19"". Neuroimmunology Reports. 3: 100154. doi:10.1016/j.nerep.2022.100154. PMC 9691274.