Buspirone

Buspirone is used for the short-term and long-term treatment of anxiety disorders or symptoms of anxiety.{{cite web|title=Buspirone HCL (buspirone hydrochloride) tablet [Watson Laboratories, Inc.]|work=DailyMed|publisher=Watson Laboratories, Inc.|date=July 2013|access-date=14 November 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a3fe0ccd-565f-4d0a-a7ba-2fad7a819358}}{{cite web|title=Buspar (buspirone hydrochloride) Tablets 5 mg & 10 mg PRODUCT INFORMATION|work=TGA eBusiness Services|publisher=Aspen Pharma Pty Ltd|date=January 2010|access-date=14 November 2013|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03962-3|format=PDF}}{{cite book | title=Australian Medicines Handbook | year=2013 | publisher=The Australian Medicines Handbook Unit Trust | isbn=978-0-9805790-9-3 | edition=2013 | place=Adelaide | veditors=Rossi S }}{{cite web |title=Buspirone 10mg Tablets |work=electronic Medicines Compendium |publisher=Actavis UK Ltd |date=10 September 2012 |access-date=14 November 2013 |url=http://www.medicines.org.uk/emc/medicine/23859/SPC/Buspirone+10mg+Tablets/|archive-date=13 November 2013|archive-url=https://web.archive.org/web/20131113191142/http://www.medicines.org.uk/emc/medicine/23859/SPC/Buspirone+10mg+Tablets/|url-status=dead}}{{cite book | last1=Joint Formulary Committee | title=British National Formulary (BNF) | publisher=Pharmaceutical Press | pages=224 }} It is generally preferred over benzodiazepines because it does not activate the receptors that make drugs like alprazolam addictive.

Buspirone has no immediate anxiolytic effects, and hence has a delayed onset of action; its full clinical effectiveness may require 2–4 weeks to manifest itself.{{cite book| vauthors=Sadock BJ, Sadock VA, Ruiz P |title=Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry |url=https://books.google.com/books?id=IzGYBAAAQBAJ&pg=PT3211|date=22 September 2014|publisher=Wolters Kluwer Health |isbn=978-1-4698-8375-5|pages=3211–}} The drug is similarly effective in the treatment of generalized anxiety disorder (GAD) to benzodiazepines including diazepam, alprazolam, lorazepam, and clorazepate. Buspirone is not known to be effective in the treatment of other anxiety disorders besides GAD.{{cite journal | vauthors=Howland RH | title=Buspirone: Back to the Future | journal=Journal of Psychosocial Nursing and Mental Health Services | volume=53 | issue=11 | pages=21–24 | date=November 2015 | pmid=26535760 | doi=10.3928/02793695-20151022-01 }}

There is some evidence that buspirone on its own may be useful in the treatment of hypoactive sexual desire disorder (HSDD) in women.{{cite journal |vauthors=Goldstein I, Kim NN, Clayton AH, DeRogatis LR, Giraldi A, Parish SJ, Pfaus J, Simon JA, Kingsberg SA, Meston C, Stahl SM, Wallen K, Worsley R |title=Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review |journal=Mayo Clinic Proceedings |volume=92 |issue=1 |pages=114–128 |date=January 2017 |pmid=27916394 |doi=10.1016/j.mayocp.2016.09.018 |doi-access=free }} Buspirone may also be effective in treating antidepressant-induced sexual dysfunction.{{cite journal |vauthors=Trinchieri M, Trinchieri M, Perletti G, Magri V, Stamatiou K, Cai T, Montanari E, Trinchieri A |title=Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review |journal=The Journal of Sexual Medicine |volume=18 |issue=8 |pages=1354–1363 |date=August 2021 |pmid=34247952 |doi=10.1016/j.jsxm.2021.05.016 |s2cid=235798526 |quote=Buspirone, a non-benzodiazepine anxiolytic, have even demonstrated enhancement of sexual function in certain individuals. For this reason, they have been proposed as augmentation agents (antidotes) or substitution agents in patients with emerging sexual dysfunction after treatment with antidepressants.}}{{cite journal |vauthors=Montejo AL, Prieto N, de Alarcón R, Casado-Espada N, de la Iglesia J, Montejo L |title=Management Strategies for Antidepressant-Related Sexual Dysfunction: A Clinical Approach |journal=Journal of Clinical Medicine |volume=8 |issue=10 |date=October 2019 |page=1640 |pmid=31591339 |pmc=6832699 |doi=10.3390/jcm8101640 |doi-access=free }}

Buspirone is not effective as a treatment for benzodiazepine withdrawal, barbiturate withdrawal, or alcohol withdrawal.{{cite journal | vauthors=Sontheimer DL, Ables AZ | title=Is imipramine or buspirone treatment effective in patients wishing to discontinue long-term benzodiazepine use? | journal=The Journal of Family Practice | volume=50 | issue=3 | pages=203 | date=March 2001 | pmid=11252203 }}

SSRI and SNRI antidepressants such as paroxetine and venlafaxine, respectively, may cause jaw pain/jaw spasm reversible syndrome, although it is not common, and buspirone appears to be successful in treating antidepressant-induced bruxism.{{cite journal | vauthors=Garrett AR, Hawley JS | title=SSRI-associated bruxism: A systematic review of published case reports | journal=Neurology. Clinical Practice | volume=8 | issue=2 | pages=135–141 | date=April 2018 | pmid=29708207 | pmc=5914744 | doi=10.1212/CPJ.0000000000000433 }}{{cite journal| vauthors=Prisco V, Iannaccone T, Di Grezia G |date=1 April 2017 |title=Use of buspirone in selective serotonin reuptake inhibitor-induced sleep bruxism|journal=European Psychiatry|series=Abstract of the 25th European Congress of Psychiatry|volume=41 |pages=S855 |doi=10.1016/j.eurpsy.2017.01.1701 |s2cid=148816505 }}

Buspirone has these contraindications:{{cite web | url= https://www.drugs.com/pro/buspirone.html | title=Buspirone monograph | publisher=Drugs.com | access-date=27 August 2011}}{{cite book | vauthors=Geddes J, Gelder MG, Mayou R | title=Psychiatry | publisher=Oxford University Press | location=Oxford [Oxfordshire] | year=2005 | page=[https://archive.org/details/psychiatry0000geld/page/237 237] | isbn=978-0-19-852863-0 | url=https://archive.org/details/psychiatry0000geld/page/237 }}

• Hypersensitivity to buspirone
• Metabolic acidosis, as in diabetes
• Should not be used with MAO inhibitors
• Severely compromised liver and/or kidney function

{{Main|List of side effects of buspirone}}

Known side effects associated with buspirone include dizziness, headaches, nausea, tinnitus, and paresthesia. Buspirone is relatively well tolerated and is not associated with sedation, cognitive and psychomotor impairment, muscle relaxation, physical dependence, or anticonvulsant effects. In addition, buspirone does not produce euphoria and is not a drug of abuse.

Buspirone appears to be relatively benign in cases of single-drug overdose, although no definitive data on this subject appear to be available.{{cite journal| vauthors=Fulton B, Brogden RN |title=Buspirone|journal=CNS Drugs|volume=7|issue=1|year=1997|pages=68–88|issn=1172-7047|doi=10.2165/00023210-199707010-00007|s2cid=57668523 }} In one clinical trial, buspirone was administered to healthy male volunteers at a dosage of 375 mg/day, and produced side effects including nausea, vomiting, dizziness, drowsiness, miosis, and gastric distress. In early clinical trials, buspirone was given at dosages even as high as 2,400 mg/day, with akathisia, tremor, and muscle rigidity observed.{{cite book| vauthors=Dart RC |title=Medical Toxicology |url= https://books.google.com/books?id=BfdighlyGiwC&pg=PA886 |year=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2845-4 |pages=886– }} Deliberate overdoses with 250 mg and up to 300 mg buspirone have resulted in drowsiness in about 50% of individuals. One death has been reported in a co-ingestion of 450 mg buspirone with alprazolam, diltiazem, alcohol, and cocaine.

Buspirone has been shown in vitro to be metabolized by the enzyme CYP3A4. This finding is consistent with the in vivo interactions observed between buspirone and these inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), among others:

• Itraconazole: Increased plasma level of buspirone
• Rifampicin: Decreased plasma levels of buspirone
• Nefazodone: Increased plasma levels of buspirone
• Haloperidol: Increased plasma levels of buspirone
• Carbamazepine: Decreased plasma levels of buspirone
• Grapefruit: Significantly increases the plasma levels of buspirone.{{cite journal | vauthors=Lilja JJ, Kivistö KT, Backman JT, Lamberg TS, Neuvonen PJ | title=Grapefruit juice substantially increases plasma concentrations of buspirone | journal=Clinical Pharmacology and Therapeutics | volume=64 | issue=6 | pages=655–660 | date=December 1998 | pmid=9871430 | doi=10.1016/S0009-9236(98)90056-X | s2cid=22009095 }} See grapefruit–drug interactions.
• Fluvoxamine: Moderately increased plasma levels of buspirone.{{cite journal | vauthors=Lamberg TS, Kivistö KT, Laitila J, Mårtensson K, Neuvonen PJ | title=The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone | journal=European Journal of Clinical Pharmacology | volume=54 | issue=9–10 | pages=761–766 | date=1998 | pmid=9923581 | doi=10.1007/s002280050548 | s2cid=21939719 }}

Elevated blood pressure has been reported when buspirone has been administered to patients taking monoamine oxidase inhibitors (MAOIs).

Buspirone has been found to markedly reduce the hallucinogenic effects of the serotonergic psychedelic psilocybin in humans.{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}{{cite journal | vauthors = Brandt SD, Kavanagh PV, Twamley B, Westphal F, Elliott SP, Wallach J, Stratford A, Klein LM, McCorvy JD, Nichols DE, Halberstadt AL | title = Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775) | journal = Drug Test Anal | volume = 10 | issue = 2 | pages = 310–322 | date = February 2018 | pmid = 28585392 | pmc = 6230476 | doi = 10.1002/dta.2222 | url = | quote = Additionally, pretreatment with the 5‐HT1A agonist buspirone (20 mg p.o.) markedly attenuates the visual effects of psilocybin in human volunteers.59 Although buspirone failed to completely block the hallucinogenic effects of psilocybin, the limited inhibition is not necessarily surprising because buspirone is a low efficacy 5‐HT1A partial agonist.60 The level of 5‐HT1A activation produced by buspirone may not be sufficient to completely counteract the stimulation of 5‐HT2A receptors by psilocin (the active metabolite of psilocybin). Another consideration is that psilocin acts as a 5‐HT1A agonist.30 If 5‐HT1A activation by psilocin buffers its hallucinogenic effects similar to DMT58 then competition between psilocin and a weaker partial agonist such as buspirone would limit attenuation of the hallucinogenic response.}}{{cite journal | vauthors = Pokorny T, Preller KH, Kraehenmann R, Vollenweider FX | title = Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience | journal = Eur Neuropsychopharmacol | volume = 26 | issue = 4 | pages = 756–766 | date = April 2016 | pmid = 26875114 | doi = 10.1016/j.euroneuro.2016.01.005 | url = }} This parallels findings in which serotonin 5-HT_1A receptor agonists like 8-OH-DPAT attenuate the head-twitch response, a behavioral proxy of psychedelic effects, induced by serotonergic psychedelics in rodents.{{cite book | vauthors = Halberstadt AL, Nichols DE | title=Handbook of Behavioral Neuroscience | chapter=Serotonin and serotonin receptors in hallucinogen action | publisher=Elsevier | volume=31 | date=2020 | isbn=978-0-444-64125-0 | doi=10.1016/b978-0-444-64125-0.00043-8 | pages=843–863}} Paradoxically however, buspirone enhances the head-twitch response, a behavioral proxy of psychedelic effects, induced by 5-hydroxytryptophan (5-HTP) plus pargyline in rodents.{{cite journal | vauthors = Haberzettl R, Bert B, Fink H, Fox MA | title = Animal models of the serotonin syndrome: a systematic review | journal = Behav Brain Res | volume = 256 | issue = | pages = 328–345 | date = November 2013 | pmid = 24004848 | doi = 10.1016/j.bbr.2013.08.045 | url = | quote = As reported in rats, studies have also demonstrated a functional relationship between 5-HT1A and 5-HT2A receptors in mice [95], [133], [186], [192]. For example, 8-OH-DPAT has been shown to attenuate head twitches induced by 5-HTP or DOI [100], [133], [162], while the partial 5-HT1A agonist buspirone has been shown to increase head twitches induced by 5-HTP plus pargyline [190].| doi-access = free }}{{cite journal | vauthors = Kitamura Y, Nagatani T, Watanabe T | title = Buspirone enhances head twitch behavior in mice | journal = Eur J Pharmacol | volume = 253 | issue = 3 | pages = 297–301 | date = March 1994 | pmid = 8200425 | doi = 10.1016/0014-2999(94)90206-2 | url = }}

Buspirone acts as a partial agonist of the serotonin 5-HT_1A receptor with high affinity. It is a partial agonist of both presynaptic 5-HT_1A receptors, which are inhibitory autoreceptors, and postsynaptic 5-HT_1A receptors. It is thought that the main effects of buspirone are mediated via its interaction with the presynaptic 5-HT_1A receptor, thus reducing the firing of serotonin-producing neurons. Buspirone also seems to have lower affinities for the serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆, 5-HT₇ receptors where it probably acts as an antagonist.

In addition to binding to serotonin receptors, buspirone is an antagonist of the dopamine D₂ receptor with weak affinity. It preferentially blocks inhibitory presynaptic D₂ autoreceptors, and antagonizes postsynaptic D₂ receptors only at higher doses. In accordance, buspirone has been found to increase dopaminergic neurotransmission in the nigrostriatal pathway at low doses, whereas at higher doses, postsynaptic D₂ receptors are blocked and antidopaminergic effects such as hypoactivity and reduced stereotypy, though notably not catalepsy, are observed in animals. Buspirone has also been found to bind with much higher affinity to the dopamine D₃ and D₄ receptors, where it is similarly an antagonist.

A major metabolite of buspirone, 1-(2-pyrimidinyl)piperazine (1-PP), occurs at higher circulating levels than buspirone itself and is known to act as a potent α₂-adrenergic receptor antagonist.{{cite journal | vauthors=Tunnicliff G | title=Molecular basis of buspirone's anxiolytic action | journal=Pharmacology & Toxicology | volume=69 | issue=3 | pages=149–156 | date=September 1991 | pmid=1796057 | doi=10.1111/j.1600-0773.1991.tb01289.x }}{{cite journal | vauthors=Zuideveld KP, Rusiç-Pavletiç J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M | title=Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats | journal=The Journal of Pharmacology and Experimental Therapeutics | volume=303 | issue=3 | pages=1130–1137 | date=December 2002 | pmid=12438536 | doi=10.1124/jpet.102.036798 | s2cid=14139919 }} This metabolite may be responsible for the increased noradrenergic and dopaminergic activity observed with buspirone in animals.{{cite journal |vauthors=Fava M |year=2007 |title=The combination of buspirone and bupropion in the treatment of depression |journal=Psychotherapy and Psychosomatics |volume=76 |issue=5 |pages=311–312 |doi=10.1159/000104708 |pmid=17700052 |s2cid=46284917}} Buspirone also has very weak and probably clinically unimportant affinity for the α₁-adrenergic receptor.{{cite book | vauthors=Stern TA, Fava M, Wilens TE, Rosenbaum JF |title= Massachusetts General Hospital Psychopharmacology and Neurotherapeutics E-Book |url= https://books.google.com/books?id=CCZ1CQAAQBAJ&pg=PA29|date=27 April 2015 |publisher= Elsevier Health Sciences |isbn= 978-0-323-41323-7 |pages=29–}} However, buspirone has been reported to have shown "significant and selective intrinsic efficacy" at the α₁-adrenergic receptor expressed in a "tissue- and species-dependent manner".

Unlike benzodiazepines, buspirone does not interact with the GABA_A receptor complex.{{cite book| vauthors=Nutt DJ, Ballenger JC |title=Anxiety Disorders|url=https://books.google.com/books?id=swAE2bRjV8UC&pg=PT395|date=15 April 2008|publisher=John Wiley & Sons|isbn=978-0-470-98683-7|pages=395–}}

Buspirone has a low oral bioavailability of 3.9% relative to intravenous injection due to extensive first-pass metabolism. The time to peak plasma levels following ingestion is 0.9 to 1.5 hours. It is reported to have an elimination half-life of 2.8 hours, although a review of 14 studies found that the mean terminal half-life ranged between 2 and 11 hours, and one study even reported a terminal half-life of 33 hours.{{cite journal | vauthors=Gammans RE, Mayol RF, LaBudde JA | title=Metabolism and disposition of buspirone | journal=The American Journal of Medicine | volume=80 | issue=3B | pages=41–51 | date=March 1986 | pmid=3515929 | doi=10.1016/0002-9343(86)90331-1 }} Buspirone is metabolized primarily by CYP3A4, and prominent drug interactions with inhibitors and inducers of this enzyme have been observed. Major metabolites of buspirone include 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-PP.{{cite journal | vauthors=Zhu Y, Chen G, Zhang K, Chen C, Chen W, Zhu M, Jiang H | title=High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach | journal=Molecules | volume=27 | issue=22 | pages=8058 | date=November 2022 | pmid=36432161 | pmc=9693510 | doi=10.3390/molecules27228058 | doi-access=free }}{{cite journal | vauthors=Wong H, Dockens RC, Pajor L, Yeola S, Grace JE, Stark AD, Taub RA, Yocca FD, Zaczek RC, Li YW | title=6-Hydroxybuspirone is a major active metabolite of buspirone: assessment of pharmacokinetics and 5-hydroxytryptamine1A receptor occupancy in rats | journal=Drug Metabolism and Disposition | volume=35 | issue=8 | pages=1387–1392 | date=August 2007 | pmid=17494642 | doi=10.1124/dmd.107.015768 | s2cid=25558546 }} 6-Hydroxybuspirone has been identified as the predominant hepatic metabolite of buspirone, with plasma levels that are 40-fold greater than those of buspirone after oral administration of buspirone to humans.{{cite book| vauthors=Schatzberg AF, Nemeroff CB |title=The American Psychiatric Publishing Textbook of Psychopharmacology |url=https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA490 |year=2009 |publisher=American Psychiatric Pub |isbn=978-1-58562-309-9 |pages=490–}} The metabolite is a high-affinity partial agonist of the 5-HT_1A receptor (K_i=25 nM) similarly to buspirone, and has demonstrated occupancy of the 5-HT_1A receptor in vivo. As such, it is likely to play an important role in the therapeutic effects of buspirone. 1-PP has also been found to circulate at higher levels than those of buspirone itself and may similarly play a significant role in the clinical effects of buspirone.

File:Buspirone metabolism.png of buspirone in humans{{cite journal | vauthors=Zhu Y, Chen G, Zhang K, Chen C, Chen W, Zhu M, Jiang H | title=High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach | journal=Molecules | volume=27 | issue=22 | pages=8058 | date=November 2022 | pmid=36432161 | pmc=9693510 | doi=10.3390/molecules27228058 | doi-access=free }}{{cite journal | vauthors=Dockens RC, Salazar DE, Fulmor IE, Wehling M, Arnold ME, Croop R | title=Pharmacokinetics of a newly identified active metabolite of buspirone after administration of buspirone over its therapeutic dose range | journal=Journal of Clinical Pharmacology | volume=46 | issue=11 | pages=1308–1312 | date=November 2006 | pmid=17050795 | doi=10.1177/0091270006292250 | s2cid=25050964 }}{{cite journal | vauthors=Jajoo HK, Mayol RF, LaBudde JA, Blair IA | title=Metabolism of the antianxiety drug buspirone in human subjects | journal=Drug Metabolism and Disposition | volume=17 | issue=6 | pages=634–640 | year=1989 | doi=10.1016/S0090-9556(25)08831-2 | pmid=2575499 }}]]

Buspirone is a member of the azapirone chemical class, and consists of azaspirodecanedione and pyrimidinylpiperazine components linked together by a butyl chain.

Structural analogues of buspirone include other azapirones like gepirone, ipsapirone, perospirone, and tandospirone.{{cite journal | vauthors=Taylor DP, Moon SL | title=Buspirone and related compounds as alternative anxiolytics | journal=Neuropeptides | volume=19 | issue=Suppl | pages=15–19 | date=July 1991 | pmid=1679210 | doi=10.1016/0143-4179(91)90078-w | s2cid=13730683 }}

A number of analogues are recorded.{{cite journal | vauthors=Yevich JP, Temple DL, New JS, Taylor DP, Riblet LA | title=Buspirone analogues. 1. Structure-activity relationships in a series of N-aryl- and heteroarylpiperazine derivatives | journal=Journal of Medicinal Chemistry | volume=26 | issue=2 | pages=194–203 | date=February 1983 | pmid=6131130 | doi=10.1021/jm00356a014 | s2cid=28619843 }}

A number of methods of synthesis have also been reported.{{cite journal | vauthors=Cybulski J, Chilmonczyk Z, Szelejewski W, Wojtasiewicz K, Wróbel JT | date=1992 | title=An Efficient Synthesis of Buspirone and its Analogues. | journal=Archiv der Pharmazie | volume=325 | issue=5 | pages=313–315 | doi=10.1002/ardp.19923250513 | s2cid=83676454 }}{{cite journal | vauthors=Kuo DL | date=1993 | title=Pd(0)-catalysed Synthesis of Buspirone and Gepirone. | journal=Heterocycles | volume=36 | issue=7 | pages=1463–1469 | doi= 10.3987/COM-93-6357 }}{{cite journal | vauthors=Mou J, Zong ZM, Wei XY |title=Facile Synthesis of Anxiolytic Buspirone |date=August 2008 |journal=Organic Preparations and Procedures International |volume=40 |issue=4 |pages=391–394 |doi=10.1080/00304940809458099 |s2cid=95124245 |issn=0030-4948 |eissn=1945-5453}} One method begins with alkylation of 1-(2-pyrimidyl)piperazine (1) with 3-chloro-1-cyanopropane (4-chlorobutyronitrile) (2) to give (3). Next, reduction of the nitrile group is performed either by catalytic hydrogenation or with lithium aluminium hydride (LAH) giving (4). The primary amine is then reacted with 3,3-tetramethyleneglutaric anhydride (5) in order to yield buspirone (6).{{cite journal | vauthors=Allen LE, Ferguson HC, Kissel JW | title=Psychosedative agents. 2. 8-(4-Substituted 1-piperazinylalkyl)-8-azaspiro(4.5)decane-7,9-diones | journal=Journal of Medicinal Chemistry | volume=15 | issue=5 | pages=477–479 | date=May 1972 | pmid=5035267 | doi=10.1021/jm00275a009 }}DE2057845 idem Y Wu, J Rayburn, {{US patent|3717634}} (1973 to Mead Johnson).{{cite patent | inventor=Wu YH, Rayburn JW | country=US | number=3907801 | gdate=1975 | assign1=Mead Johnson}}{{cite patent | inventor=Wu YH, Rayburn JW | country=US | number=3976776 | gdate=1976 | assign1=Mead Johnson}}{{cite patent | inventor=Behme RJ, Kensler TT, Mikolasek DG | country=US | number=4810789 | gdate=1989 | assign1=Bristol Myers}}

File:Buspirone-synthesis.svg {{clear-left}}

Buspirone was first synthesized by a team at Mead Johnson in 1968 but was not patented until 1980.{{cite patent|country=US |number=4182763 |title=Buspirone anti-anxiety method |pubdate=1980-01-08 |inventor=Casten GP, McKinney GR, Newton RE, Tompkins EC, Weikel Jr JH |assign1=Mead Johnson & Co.|assign2=Bristol-Meyers Co.}}{{cite patent |country=US |number=3907801| pubdate=1975-09-23 |title=N-[(4-pyridyl-piperazino)-alkyl]-azaspiroalkanediones |assign=Mead_Johnson| inventor=Hua WY, Warren RJ }} It was initially developed as an antipsychotic acting on the D₂ receptor but was found to be ineffective in the treatment of psychosis; it was then used as an anxiolytic instead. In 1986, Bristol-Myers Squibb gained FDA approval for buspirone in the treatment of GAD.{{cite web | publisher=United States Federal Drug Administration | date=9 September 1986 | title=Approval Type-1 New Molecular Entry. | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/018731Orig1s000rev.pdf }} The patent expired in 2001, and buspirone is now available as a generic drug.

File:Buspar.jpg

Buspirone is the {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|DCIT|Denominazione Comune Italiana}} of buspirone, while buspirone hydrochloride is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.{{cite book| vauthors=Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA192 |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=192–}}{{cite book |title=Index Nominum 2000: International Drug Directory |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA149|date=January 2000|publisher=Taylor & Francis | isbn=978-3-88763-075-1|pages=149–}}{{cite book| vauthors=Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms |url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA57|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=57–}}{{cite web | url=https://www.drugs.com/international/buspirone.html |title=Buspirone | work=Drugs.com }}

Buspirone was primarily sold under the brand name Buspar. Buspar is currently listed as discontinued by the U.S. Food and Drug Administration (FDA).{{cite web | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=018731 |title=Drugs@FDA: FDA Approved Drug Products| publisher=Food and Drug Administration}} In 2010, in response to a citizen petition, the FDA determined that Buspar was not withdrawn from sale for reasons of safety or effectiveness.{{cite web|url=https://www.federalregister.gov/documents/2010/10/19/2010-26214/determination-that-buspar-buspirone-hydrochloride-tablets-10-milligrams-15-milligrams-and-30|title=Determination That Buspar (Buspirone Hydrochloride) Tablets, 10 Milligrams, 15 Milligrams, and 30 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness|date=19 October 2010|website=Federal Register|access-date=20 September 2019}}

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