Guanfacine Explained

Verifiedfields:changed
Verifiedrevid:461124228
Class:Centrally acting α2A- adrenergic receptor agonist
Tradename:Estulic, Intuniv, Tenex, others
Dailymedid:Guanfacine
Routes Of Administration:By mouth
Atc Prefix:C02
Atc Suffix:AC02
Legal Au:S4
Legal Au Comment:[1] [2]
Legal Ca:Rx-only
Legal Us:Rx-only
Legal Us Comment:[3]
Legal Eu:Rx-only
Legal Eu Comment:[4]
Bioavailability:80–100% (IR), 58% (XR)[5] [6]
Protein Bound:70%
Metabolism:CYP3A4
Elimination Half-Life:IR: 10–17 hours; XR: 17 hours (10–30) in adults & adolescents and 14 hours in children[7] [8]
Excretion:Kidney (80%; 50% [range: 40–75%] as unchanged drug)
Cas Number:29110-47-2
Pubchem:3519
Iuphar Ligand:522
Drugbank:DB01018
Chemspiderid:3399
Unii:30OMY4G3MK
Kegg:D08031
Chembl:862
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: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:INJOMKTZOLKMBF-UHFFFAOYSA-N

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.[9] Guanfacine is FDA-approved for monotherapy treatment of ADHD, as well as being used for augmentation of other treatments, such as stimulants. Guanfacine is also used off-label to treat tic disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).[10]

Common side effects include sleepiness, constipation, and dry mouth.[9] Other side effects may include low blood pressure and urinary problems.[11] 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.[12] [11] It appears to work by activating α2A-adrenergic receptors in the brain, thereby decreasing sympathetic nervous system activity.[9]

Guanfacine was first described by 1974 and was approved for medical use in the United States in 1986.[9] It is available as a generic medication.[9] In 2021, it was the 231st most commonly prescribed medication in the United States, with more than 1million prescriptions.[13] [14]

Medical uses

Guanfacine is FDA-approved as monotherapy or augmentation with stimulants to treat attention deficit hyperactivity disorder (ADHD).[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. 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.[9] For ADHD, it is claimed that guanfacine helps individuals better control behavior, inhibit inappropriate distractions and impulses, and inhibit inappropriate aggressive impulses. 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).[18] [19] [20] 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.[21] In any case, guanfacine and other α2-adrenergic receptor agonists are considered to be less effective than stimulants in the treatment of ADHD.[22]

Guanfacine is also used off-label to treat tic disorders, anxiety disorders such as generalized anxiety disorder, and PTSD.[10] Guanfacine and other α2A-adrenergic receptor agonists have anxiolytic-like action,[23] thereby reducing the emotional responses of the amygdala, and strengthening prefrontal cortical regulation of emotion, action, and thought. These actions arise from both inhibition of stress-induced catecholamine release, and from prominent, post-synaptic actions in the prefrontal cortex.[24] Due to its prolonged elimination half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients.[25] All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD.[26] Guanfacine appears to be especially helpful in treating children who have been traumatized or abused.

Adverse effects

Side effects of guanfacine are dose-dependent.[27]

Very common (>10% incidence) adverse effects include sleepiness, tiredness, headache, and stomach ache.[28]

Common (1–10% incidence) adverse effects include decreased appetite, nausea, dry mouth, urinary incontinence, and rashes.[28]

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.

Guanfacine may worsen sleep in children with ADHD, including reduced total sleep time.[29]

A 2020 systematic review found side effects of guanfacine including abdominal pain, sedation, and QT prolongation.[30]

Interactions

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.[28]

Pharmacology

Pharmacodynamics

Guanfacine
Site Ki (nM) Species Ref
50.3 – 93.3 Human [31] [32]
1,020 – 1,380 Human
1,120 – 3,890 Human
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.[34] [35] [36] [37]

Guanfacine works by activating α2A-adrenoceptors[38] 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.[39]

In ADHD, guanfacine is thought to work by strengthening the regulation of attention and behavior by the prefrontal cortex.[40] 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. Cyclic adenosine monophosphate (cAMP)-mediated opening of HCN and KCNQ channels is inhibited, which enhances prefrontal cortical synaptic connectivity and neuronal firing.[41] In monkeys, guanfacine improves working memory, attention regulation, and behavioral inhibition, and these actions are independent of its sedative effects. The use of guanfacine for treating prefrontal disorders was developed by the Arnsten Lab at Yale University.[42]

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. 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).

Activation of the 5-HT2B receptor is a well-known antitarget and is associated with cardiac valvulopathy. However, not all 5-HT2B receptor agonists, for instance ropinirole, have this effect. 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.[43] [44] 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. 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. In any case, different studies have reported different potencies of guanfacine as a 5-HT2B receptor agonist, and as of 2018, no clinical data on the risk of cardiac valvulopathy with guanfacine were available.[45] As such, while the likelihood is thought to be low, guanfacine might still have a risk of cardiac valvulopathy.

Guanfacine has been found to act as an agonist of the trace amine-associated receptor 1 (TAAR1).[46]

Pharmacokinetics

Guanfacine has an oral bioavailability of 80%. There is no clear evidence of any first-pass metabolism. Its elimination half-life is 17hours 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]

Preparation

Guanfacine can be prepared from equal parts and guanidine:[49]

History

Guanfacine was first described in the literature by 1974.[50] [51] [52] [53] [54] In 1986, guanfacine was approved by the FDA for the treatment of hypertension under the brand name Tenex.[55] In 2010, guanfacine was approved by the FDA for the treatment of attention deficit hyperactivity disorder for people 6 to 17 years old. It was approved for ADHD by the European Medicines Agency under the name Intuniv in 2015.[56] It was added to the Australian Pharmaceutical Benefits Scheme for the treatment of ADHD in 2018.[57]

Society and culture

Brand names

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

Research

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.[58] It may be also useful in adult PTSD patients who do not respond to selective serotonin reuptake inhibitors (SSRIs).[59]

Results of studies using guanfacine to treat Tourette's syndrome have been mixed.[60]

Guanfacine does not appear to be effective for improving sleep in children with ADHD and behavioral insomnia.[61] Instead, guanfacine worsened certain sleep parameters, for instance total sleep time, in one clinical trial.

Guanfacine has been investigated for treatment of withdrawal for opioids, ethanol, and nicotine.[62] 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.[63]

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.[64]

Guanfacine is being studied for the possible treatment of long COVID.[65] [66] [67]

Notes and References

  1. Web site: Prescription medicines: registration of new chemical entities in Australia, 2017 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 9 April 2023.
  2. Web site: Prescription medicines and biologicals: TGA annual summary 2017 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 31 March 2024.
  3. Web site: 26 January 2021 . Intuniv- guanfacine tablet, extended release Intuniv- guanfacine kit . 6 August 2022 . DailyMed . 6 August 2022 . https://web.archive.org/web/20220806051328/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528 . live .
  4. Web site: Intuniv EPAR . European Medicines Agency . 17 September 2015 . 13 June 2024.
  5. Web site: March 2007 . Guanfacine (guanfacine) Tablet [Genpharm Inc.] ]. 9 November 2013 . DailyMed . Genpharm Inc. . 26 June 2022 . https://web.archive.org/web/20220626115201/https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9fc0bdc2-5ba2-48dd-aa87-7b0050a2d6ce . live .
  6. Web site: guanfacine (Rx) - Intuniv, Tenex . 9 November 2013 . Medscape Reference . WebMD . 18 May 2019 . https://web.archive.org/web/20190518174636/https://reference.medscape.com/drug/intuniv-tenex-guanfacine-342384 . live .
  7. Hofer KN, Buck ML . 2008 . New Treatment Options for Attention-Deficit/Hyperactivity Disorder (ADHD): Part II. Guanfacine . Pediatric Pharmacotherapy . 14 . 4 . 30 July 2014 . 31 October 2015 . https://web.archive.org/web/20151031172657/http://www.medscape.com/viewarticle/578747_4 . live .
  8. 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 . 2935643 . 20844694.
  9. Web site: Guanfacine Monograph for Professionals . https://web.archive.org/web/20180115071707/https://www.drugs.com/monograph/guanfacine.html . 15 January 2018 . 18 March 2019 . Drugs.com . American Society of Health-System Pharmacists . en.
  10. Book: Boland RJ, Verduin ML, Sadock BJ . Kaplan & Sadock's Concise Textbook of Clinical Psychiatry . 2023 . 978-1-9751-6748-6 . Ruiz P . 5th . Philadelphia . Wolters Kluwer . 1811–1812 . 1264172789 . 12 January 2023 . 8 February 2023 . https://web.archive.org/web/20230208191429/https://www.worldcat.org/title/1264172789 . live .
  11. Book: British national formulary: BNF 76 . 2018 . Pharmaceutical Press . 978-0-85711-338-2 . 76 . 349–350.
  12. Web site: Patient Information. INTUNIV (in-TOO-niv) (guanfacine). Extended-Release Tablets . FDA.gov . 12 October 2022 . 13 October 2022 . https://web.archive.org/web/20221013031444/https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022037s002lbl.pdf . live .
  13. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  14. Web site: Guanfacine - Drug Usage Statistics . ClinCalc . 14 January 2024.
  15. Kornfield R, Watson S, Higashi AS, Conti RM, Dusetzina SB, Garfield CF, Dorsey ER, Huskamp HA, Alexander GC . April 2013 . Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008 . Psychiatric Services . 64 . 4 . 339–346 . 10.1176/appi.ps.201200147 . 4023684 . 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 . 10.1186/1753-2000-2-24 . 2566553 . 18793403 . free . doi.
  17. Clemow DB, Walker DJ . The potential for misuse and abuse of medications in ADHD: a review . Postgraduate Medicine . 126 . 5 . 64–81 . September 2014 . 25295651 . 10.3810/pgm.2014.09.2801 . 207580823 .
  18. Radonjić NV, Bellato A, Khoury NM, Cortese S, Faraone SV . Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-analysis . CNS Drugs . 37 . 5 . 381–397 . May 2023 . 37166701 . 10.1007/s40263-023-01005-8 . 258616507 .
  19. Yu S, Shen S, Tao M . Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis . J Child Adolesc Psychopharmacol . 33 . 2 . 40–50 . March 2023 . 36944092 . 10.1089/cap.2022.0038 . 257664282 .
  20. Catalá-López F, Hutton B, Núñez-Beltrán A, Page MJ, Ridao M, Macías Saint-Gerons D, Catalá MA, Tabarés-Seisdedos R, Moher D . 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 . 2017 . 28700715 . 5507500 . 10.1371/journal.pone.0180355 . free . 2017PLoSO..1280355C .
  21. Pringsheim T, Hirsch L, Gardner D, Gorman DA . 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 . February 2015 . 25886655 . 4344946 . 10.1177/070674371506000202 .
  22. Padilha SC, Virtuoso S, Tonin FS, Borba HH, Pontarolo R . 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 . October 2018 . 29460165 . 10.1007/s00787-018-1125-0 . 3402756 .
  23. Morrow BA, George TP, Roth RH . Noradrenergic alpha-2 agonists have anxiolytic-like actions on stress-related behavior and mesoprefrontal dopamine biochemistry . Brain Research . 1027 . 1–2 . 173–178 . November 2004 . 15494168 . 10.1016/j.brainres.2004.08.057 . 7066842 .
  24. Arnsten AF, Raskind MA, Taylor FB, Connor DF . 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 . January 2015 . 25436222 . 4244027 . 10.1016/j.ynstr.2014.10.002 .
  25. Kozaric-Kovacic D . Psychopharmacotherapy of posttraumatic stress disorder . Croatian Medical Journal . 49 . 4 . 459–475 . August 2008 . 18716993 . 2525822 . 10.3325/cmj.2008.4.459 .
  26. Kaminer D, Seedat S, Stein DJ . Post-traumatic stress disorder in children . World Psychiatry . 4 . 2 . 121–125 . June 2005 . 16633528 . 1414752 .
  27. 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 . 10.1111/j.1365-2125.1980.tb04924.x . 1430125 . 6994770.
  28. Web site: June 2017 . Intuniv 1 mg, 2 mg, 3 mg, 4 mg prolonged-release tablets - Summary of Product Characteristics . UK Electronic Medicines Compendium . 7 July 2017 . 15 January 2018 . https://web.archive.org/web/20180115184531/https://www.medicines.org.uk/emc/medicine/31294 . dead .
  29. Rugino TA . Effect on Primary Sleep Disorders When Children With ADHD Are Administered Guanfacine Extended Release . J Atten Disord . 22 . 1 . 14–24 . January 2018 . 25376194. 10.1177/1087054714554932 . 22675882 .
  30. Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU . 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 . June 2020 . 32394557 . 7215080 . 10.1002/wps.20765 .
  31. Jasper JR, Lesnick JD, Chang LK, Yamanishi SS, Chang TK, Hsu SA, Daunt DA, Bonhaus DW, Eglen RM . April 1998 . Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding . Biochemical Pharmacology . 55 . 7 . 1035–1043 . 10.1016/s0006-2952(97)00631-x . 9605427.
  32. 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 . 7996470.
  33. Web site: Bryan Roth . 12 January 2011 . PDSP Ki Database . dead . https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php . 8 November 2013 . 15 November 2013 . Psychoactive Drug Screening Program (PDSP) . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . Roth BL, Driscol J.
  34. Bender AM, Parr LC, Livingston WB, Lindsley CW, Merryman WD . 2B Determined: The Future of the Serotonin Receptor 2B in Drug Discovery . J Med Chem . 66 . 16 . 11027–11039 . August 2023 . 37584406 . 10.1021/acs.jmedchem.3c01178 . 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. 11073569 .
  35. Hutcheson JD, Setola V, Roth BL, Merryman WD . Serotonin receptors and heart valve disease--it was meant 2B . Pharmacol Ther . 132 . 2 . 146–57 . November 2011 . 21440001 . 3179857 . 10.1016/j.pharmthera.2011.03.008 .
  36. Huang XP, Setola V, Yadav PN, Allen JA, Rogan SC, Hanson BJ, Revankar C, Robers M, Doucette C, Roth BL . 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 . 10.1124/mol.109.058057 . 2769050 . 19570945.
  37. 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 . Kinetics of 5-HT2B receptor signaling: profound agonist-dependent effects on signaling onset and duration . J Pharmacol Exp Ther . 347 . 3 . 645–59 . December 2013 . 24049061 . 10.1124/jpet.113.207670 . 8013309 .
  38. 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.
  39. 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 . 10.1111/j.1365-2125.1983.tb00311.x . 1427667 . 7433512.
  40. Arnsten AF . The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder . Expert Review of Neurotherapeutics . 10 . 10 . 1595–1605 . October 2010 . 20925474 . 3143019 . 10.1586/ern.10.133 .
  41. 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 . April 2007 . Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex . Cell . 129 . 2 . 397–410 . 10.1016/j.cell.2007.03.015 . 17448997 . free . 741677.
  42. 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 . 3313539 . 22461743.
  43. Web site: Australian Public Assessment Report for Guanfacine (as hydrochloride) . Therapeutic Goods Administration . May 2018.
  44. 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
  45. Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, Mladěnka A, Karlíčková J, Jahodář L, Vopršalová M, Varner KJ, Štěrba M . Comprehensive review of cardiovascular toxicity of drugs and related agents . Med Res Rev . 38 . 4 . 1332–1403 . July 2018 . 29315692 . 6033155 . 10.1002/med.21476 . 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.
  46. Cichero E, Francesconi V, Casini B, Casale M, Kanov E, Gerasimov AS, Sukhanov I, Savchenko A, Espinoza S, Gainetdinov RR, Tonelli M . Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays . Pharmaceuticals . 16 . 11 . November 2023 . 1632 . 38004497 . 10674299 . 10.3390/ph16111632 . free .
  47. Kiechel JR . 1980 . Pharmacokinetics and metabolism of guanfacine in man: a review . British Journal of Clinical Pharmacology . 10 . Suppl 1 . 25S–32S . 10.1111/j.1365-2125.1980.tb04901.x . 1430131 . 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 . 10.1111/j.1365-2125.1980.tb04902.x . 1430110 . 6994776.
  49. US3632645A. Substituted phenylacetyl derivatives of guanidine o-alkylisoureas s-alkylisothioureas and p-nitrobenzylisothiourea. 1972-01-04. Bream. Picard. John Bernard. Claude W..
  50. Turner, A. S. (1974). BS 100-141 in the treatment of arterial hypertension. Seventh World Congr. of Cardiol., Abstr, 336.
  51. Scholtysik G . 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 . 1974 . 4276642 .
  52. Bream JB, Lauener H, Picard CW, Scholtysik G, White TG . Substituted phenylacetylguanidines: a new class of antihypertensive agents . Arzneimittelforschung . 25 . 10 . 1477–82 . October 1975 . 1243024 .
  53. Saameli K, Scholtysik G, Waite R . Pharmacology of BS 100-141, a centrally acting antihypertensive drug . Clinical and Experimental Pharmacology & Physiology . 1975 . Suppl 2 . 207–212 . 1975 . 241524 .
  54. Dubach UC, Huwyler R, Radielovic P, Singeisen M . A new centrally action antihypertensive agent guanfacine (BS 100-141) . Arzneimittelforschung . 27 . 3 . 674–6 . 1977 . 326262 .
  55. Web site: Drugs@FDA: FDA-Approved Drugs .
  56. Web site: October 2015 . European Medicines Agency: Intuniv . Europa (web portal) . 3 February 2016 . 16 August 2018 . 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 . live .
  57. News: New drugs listed on the PBS for rheumatoid arthritis, cystic fibrosis and ADHD . Newsgp . 11 September 2018 . Royal Australian College of General Practitioners . 11 September 2018 . https://web.archive.org/web/20180911114443/https://www.racgp.org.au/newsGP/Clinical/New-drugs-listed-on-the-PBS-for-rheumatoid-arthrit . live .
  58. 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 . 10.1089/cap.2012.0119 . 3657282 . 23683139.
  59. Belkin MR, Schwartz TL . 2015 . Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder . Drugs in Context . 4 . 212286 . 10.7573/dic.212286 . 4544272 . 26322115.
  60. 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 . 2527768 . 18769586.
  61. Anand S, Tong H, Besag FM, Chan EW, Cortese S, Wong IC . 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 . June 2017 . 28391425 . 10.1007/s40272-017-0224-6 . 2220464 .
  62. Sofuoglu M, Sewell RA . April 2009 . Norepinephrine and stimulant addiction . Addiction Biology . 14 . 2 . 119–129 . 10.1111/j.1369-1600.2008.00138.x . 2657197 . 18811678.
  63. McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten AF, Picciotto MR, Weinberger AH, Ashare R, Sinha R . March 2015 . A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation . Journal of Psychopharmacology . 29 . 3 . 300–311 . 10.1177/0269881114562091 . 4376109 . 25516371.
  64. Arnsten AF . Guanfacine's mechanism of action in treating prefrontal cortical disorders: Successful translation across species . Neurobiol Learn Mem . 176 . 107327 . December 2020 . 33075480 . 7567669 . 10.1016/j.nlm.2020.107327 .
  65. Fesharaki Zadeh A, Arnsten AF, Wang M . Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID . Neurol Int . 15 . 2 . 725–742 . May 2023 . 37368329 . 10303664 . 10.3390/neurolint15020045 . free .
  66. Arnsten AF, Ishizawa Y, Xie Z . Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders . Mol Psychiatry . 28. 11. 4540–4552 . April 2023 . 37029295 . 10080530 . 10.1038/s41380-023-02057-4 .
  67. Reiken S, Sittenfeld L, Dridi H, Liu Y, Liu X, Marks AR . Alzheimer's-like signaling in brains of COVID-19 patients . Alzheimer's & Dementia . 18 . 5 . 955–965 . May 2022 . 9691274 . 10.1016/j.nerep.2022.100154 .

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