fbpx
Wikipedia

Buspirone

January 26, 2023

Not to be confused with Bupropion.

Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder.[9][10] Benefits support its short-term use.[11] It is taken by mouth, and it may take up to four weeks to have an effect.[9][10]

Buspirone
Clinical data
Pronunciation/ˈbjuːspɪroʊn/ (BEW-spi-rohn)
Trade namesBuspar, Namanspin
Other namesMJ 9022-1[1]
AHFS/Drugs.comMonograph
MedlinePlusa688005
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability3.9%[2]
Protein binding86–95%[3]
MetabolismLiver (via CYP3A4)[7][8]
Metabolites5-OH-Buspirone; 6-OH-Buspirone; 8-OH-Buspirone; 1-PP[4][5][6]
Elimination half-life2.5 hours[7]
ExcretionUrine: 29–63%[3]
Feces: 18–38%[3]
Identifiers
  • 8-{4-[4-(Pyrimidin-2-yl)piperazin-1-yl]butyl}-8-azaspiro[4.5]decane-7,9-dione
CAS Number
PubChem CID
  • 2477
IUPHAR/BPS
  • 36
DrugBank
  • DB00490 Y
ChemSpider
  • 2383 Y
UNII
  • TK65WKS8HL
KEGG
  • D07593 Y
ChEBI
  • CHEBI:3223 Y
ChEMBL
  • ChEMBL49 Y
CompTox Dashboard (EPA)
  • DTXSID2022707
ECHA InfoCard100.048.232
Chemical and physical data
FormulaC21H31N5O2
Molar mass385.512 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C1CC2(CCCC2)CC(=O)N1CCCCN1CCN(c2ncccn2)CC1
  • InChI=1S/C21H31N5O2/c27-18-16-21(6-1-2-7-21)17-19(28)26(18)11-4-3-10-24-12-14-25(15-13-24)20-22-8-5-9-23-20/h5,8-9H,1-4,6-7,10-17H2 Y
  • Key:QWCRAEMEVRGPNT-UHFFFAOYSA-N Y
  (verify)

Common side effects of buspirone include nausea, headaches, dizziness, and difficulty concentrating.[9][11] Serious side effects may include hallucinations, serotonin syndrome, and seizures.[11] Its use in pregnancy appears to be safe but has not been well studied, while use during breastfeeding has not been well studied.[11][12] It is a serotonin 5-HT1A receptor agonist.[2]

Buspirone was first made in 1968 and approved for medical use in the United States in 1986.[9][10] It is available as a generic medication.[11] In 2020, it was the 55th most-commonly prescribed medication in the United States, with more than 12 million prescriptions.[13][14]

Medical uses

Anxiety

Buspirone is used for the short-term and long-term treatment of anxiety disorders or symptoms of anxiety.[15][16][17][18][19] It is generally preferred over benzodiazepines because it does not activate the receptors that make drugs like alprazolam addictive.[10]

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.[20] The drug has been shown to be similarly effective in the treatment of generalized anxiety disorder (GAD) to benzodiazepines including diazepam, alprazolam, lorazepam, and clorazepate.[2] Buspirone is not known to be effective in the treatment of other anxiety disorders besides GAD,[21] although there is some limited evidence that it may be useful in the treatment of social phobia as an adjunct to selective serotonin reuptake inhibitors (SSRIs).[2][22]

Other uses

Sexual dysfunction

There is some evidence that buspirone on its own may be useful in the treatment of hypoactive sexual desire disorder (HSDD) in women.[23]

Miscellaneous

Buspirone is not effective as a treatment for benzodiazepine withdrawal, barbiturate withdrawal, or alcohol withdrawal/delirium tremens.[24]

SSRI and SNRI antidepressants such as paroxetine and venlafaxine may cause jaw pain/jaw spasm reversible syndrome (although it is not common), and buspirone appears to be successful in treating bruxism on SSRI/SNRI-induced jaw clenching.[25][26]

Contraindications

Buspirone has these contraindications:[27][28]

Side effects

Main article: List of side effects of buspirone

Known side effects associated with buspirone include dizziness, headaches, nausea, tinnitus, and paresthesia.[2] Buspirone is relatively well tolerated, and is not associated with sedation, cognitive and psychomotor impairment, muscle relaxation, physical dependence, or anticonvulsant effects.[2] In addition, buspirone does not produce euphoria[20] and is not a drug of abuse.[16] Dyskinesia, akathisia, myoclonus, parkinsonism, and dystonia were reported associated with buspirone.[29] It is unclear if there is a risk of tardive dyskinesia or other movement disorders with buspirone.[9]

Overdose

Buspirone appears to be relatively benign in cases of single-drug overdose, although no definitive data on this subject appear to be available.[30] 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.[15][16][18] In early clinical trials, buspirone was given at dosages even as high as 2,400 mg/day, with akathisia, tremor, and muscle rigidity observed.[31] Deliberate overdoses with 250 mg and up to 300 mg buspirone have resulted in drowsiness in about 50% of individuals.[31] One death has been reported in a co-ingestion of 450 mg buspirone with alprazolam, diltiazem, alcohol, cocaine.[31]

Interactions

Buspirone has been shown in vitro to be metabolized by the enzyme CYP3A4.[8] This finding is consistent with the in vivo interactions observed between buspirone and these inhibitors or inducers of cytochrome P450 3A4 (CYP3A4), among others:[27]

Elevated blood pressure has been reported when buspirone has been administered to patients taking monoamine oxidase inhibitors (MAOIs).[27]

Pharmacology

Pharmacodynamics

Buspirone[34]
Site Ki (nM) Species Ref
5-HT1A 3.98–214
21 (median)		 Human [34][35]
5-HT1B >100,000 Rat [36]
5-HT1D 22,000–42,700 Human [37][38]
5-HT2A 138
759–1,300		 Human
Rat		 [39]
[36][39]
5-HT2B 214 Human [39]
5-HT2C 490
1,100–6,026		 Human
Rat/pig		 [39]
[36][39]
5-HT3 >10,000 Rat [40][41]
5-HT4 >10,000 Rat [41]
5-HT6 398 Mouse [42]
5-HT7 375–381
840		 Rat
Human		 [43][44]
[45]
α1 1,000 Rat [36]
α2 6,000 Rat [46]
  α2A 7.3 (1-PP) Human [36]
β 8,800 Rat [36]
D1 33,000 Rat [36]
D2 484
240		 Human
Rat		 [47]
[36]
D3 98 Human [47]
D4 29 Human [47]
mACh 38,000 Rat [36]
GABAA
(BDZ)		 >100,000 Rat [36]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Buspirone acts as an agonist of the serotonin 5-HT1A receptor with high affinity.[2][36] It is a partial agonist of both presynaptic 5-HT1A receptors, which are inhibitory autoreceptors, and postsynaptic 5-HT1A receptors.[2] It is thought that the main effects of buspirone are mediated via its interaction with the presynaptic 5-HT1A receptor, thus reducing the firing of serotonin-producing neurons.[2] Buspirone also has lower affinities for the serotonin 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6, and 5-HT7 receptors.[34]

In addition to binding to serotonin receptors, buspirone is an antagonist of the dopamine D2 receptor with weak affinity.[2][36] It preferentially blocks inhibitory presynaptic D2 autoreceptors, and antagonizes postsynaptic D2 receptors only at higher doses.[2] 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.[2] Buspirone has also been found to bind with much higher affinity to the dopamine D3 and D4 receptors, where it is similarly an antagonist.[47]

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.[46][48][49] This metabolite may be responsible for the increased noradrenergic and dopaminergic activity observed with buspirone in animals.[48][50] In addition, 1-PP may play an important role in the antidepressant effects of buspirone.[50] Buspirone also has very weak and probably clinically unimportant affinity for the α1-adrenergic receptor.[36][51] 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".[51]

Unlike benzodiazepines, buspirone does not interact with the GABAA receptor complex.[2][52]

Pharmacokinetics

Buspirone has a low oral bioavailability of 3.9% relative to intravenous injection due to extensive first-pass metabolism.[2] The time to peak plasma levels following ingestion is 0.9 to 1.5 hours.[2] It is reported to have an elimination half-life of 2.8 hours,[2] 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.[4] Buspirone is metabolized primarily by CYP3A4, and prominent drug interactions with inhibitors and inducers of this enzyme have been observed.[7][8] Major metabolites of buspirone include 5-hydroxybuspirone, 6-hydroxybuspirone, 8-hydroxybuspirone, and 1-PP.[53][4][5][6] 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.[5] The metabolite is a high-affinity partial agonist of the 5-HT1A receptor (Ki = 25 nM) similarly to buspirone, and has demonstrated occupancy of the 5-HT1A receptor in vivo.[5] As such, it is likely to play an important role in the therapeutic effects of buspirone.[5] 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.[48][50]

 
Phase I Metabolism of buspirone in humans[54][55][56][8]

Chemistry

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

Analogues

Structural analogues of buspirone include other azapirones like gepirone, ipsapirone, perospirone, and tandospirone.[57]

A number of analogues are recorded.[58]

Synthesis

A number of more modern methods of synthesis have also been reported (list not exhaustive):[59][60][61]

 
Synthesis:[62] Patents:[63][64][65] Polymorphic crystalline form:[66]

Alkylation of 1-(2-pyrimidyl)piperazine [20980-22-7] (1) with 3-chloro-1-cyanopropane (4-chlorobutyronitrile) [628-20-6] (2) gives [33386-14-0] (3). the reduction of the nitrile group is performed either by catalytic hydrogenation or with LAH giving [33386-20-8] (4). The primary amine is then reacted with 3,3-tetramethyleneglutaric anhydride [5662-95-3] (5) in order to yield Buspirone (6).

History

Buspirone was first synthesized by a team at Mead Johnson in 1968[21] but was not patented until 1980.[67][62][68] 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.[2] In 1986, Bristol-Myers Squibb gained FDA approval for buspirone in the treatment of GAD.[21][69] The patent expired in 2001, and buspirone is now available as a generic drug.

Society and culture

 
Buspar (buspirone) 10-mg tablets

Generic names

Buspirone is the INN, BAN, DCF, and DCIT of buspirone, while buspirone hydrochloride is its USAN, BANM, and JAN.[1][70][71][72]

Brand name

Buspirone was primarily sold under the brand name Buspar.[70][72] Buspar is currently listed as discontinued by the US Federal Drug Administration.[73] In 2010, in response to a citizen petition, the US FDA determined that Buspar was not withdrawn from sale for reasons of safety or effectiveness.[74]

2019 shortage

Due to interrupted production at a Mylan Pharmaceuticals plant in Morgantown, West Virginia, the United States experienced a shortage of buspirone in 2019.[75]

Research

Some tentative research supports other uses such as the treatment of depression and behavioral problems following brain damage.[2]

References

  1. ^ a b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 192–. ISBN 978-1-4757-2085-3.
  2. ^ a b c d e f g h i j k l m n o p q r Loane C, Politis M (June 2012). "Buspirone: what is it all about?". Brain Research. 1461: 111–118. doi:10.1016/j.brainres.2012.04.032. PMID 22608068. S2CID 11734819.
  3. ^ a b c "buspirone (Rx) - BuSpar, Buspirex, more." Medscape Reference. WebMD. Retrieved 14 November 2013.
  4. ^ a b c Gammans RE, Mayol RF, LaBudde JA (March 1986). "Metabolism and disposition of buspirone". The American Journal of Medicine. 80 (3B): 41–51. doi:10.1016/0002-9343(86)90331-1. PMID 3515929.
  5. ^ a b c d e Schatzberg AF, Nemeroff CB (2009). The American Psychiatric Publishing Textbook of Psychopharmacology. American Psychiatric Pub. pp. 490–. ISBN 978-1-58562-309-9.
  6. ^ a b Wong H, Dockens RC, Pajor L, Yeola S, Grace JE, Stark AD, et al. (August 2007). "6-Hydroxybuspirone is a major active metabolite of buspirone: assessment of pharmacokinetics and 5-hydroxytryptamine1A receptor occupancy in rats". Drug Metabolism and Disposition. 35 (8): 1387–1392. doi:10.1124/dmd.107.015768. PMID 17494642. S2CID 25558546.
  7. ^ a b c Mahmood I, Sahajwalla C (April 1999). "Clinical pharmacokinetics and pharmacodynamics of buspirone, an anxiolytic drug". Clinical Pharmacokinetics. 36 (4): 277–287. doi:10.2165/00003088-199936040-00003. PMID 10320950. S2CID 1102318.
  8. ^ a b c d Zhu M, Zhao W, Jimenez H, Zhang D, Yeola S, Dai R, et al. (April 2005). "Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes". Drug Metabolism and Disposition. 33 (4): 500–507. doi:10.1124/dmd.104.000836. PMID 15640381. S2CID 10142905.
  9. ^ a b c d e "Buspirone Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  10. ^ a b c d Wilson TK, Tripp J (January 2018). "Buspirone". StatPearls. PMID 30285372.
  11. ^ a b c d e British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 338. ISBN 9780857113382.
  12. ^ "Buspirone Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  13. ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  14. ^ "Buspirone - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  15. ^ a b "BUSPIRONE HCL (buspirone hydrochloride) tablet [Watson Laboratories, Inc.]". DailyMed. Watson Laboratories, Inc. July 2013. Retrieved 14 November 2013.
  16. ^ a b c "BUSPAR® (buspirone hydrochloride) Tablets 5 mg & 10 mg PRODUCT INFORMATION" (PDF). TGA eBusiness Services. Aspen Pharma Pty Ltd. January 2010. Retrieved 14 November 2013.
  17. ^ Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  18. ^ a b "Buspirone 10mg Tablets". electronic Medicines Compendium. Actavis UK Ltd. 10 September 2012. Retrieved 14 November 2013.
  19. ^ Joint Formulary Committee. British National Formulary (BNF). Pharmaceutical Press. p. 224.
  20. ^ a b Sadock BJ, Sadock VA, Ruiz P (22 September 2014). Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Wolters Kluwer Health. pp. 3211–. ISBN 978-1-4698-8375-5.
  21. ^ a b c Howland RH (November 2015). "Buspirone: Back to the Future". Journal of Psychosocial Nursing and Mental Health Services. 53 (11): 21–24. doi:10.3928/02793695-20151022-01. PMID 26535760.
  22. ^ Masdrakis VG, Turic D, Baldwin DS (2013). "Pharmacological treatment of social anxiety disorder". Anxiety Disorders. Modern Trends in Pharmacopsychiatry. Vol. 29. pp. 144–53. doi:10.1159/000351960. ISBN 978-3-318-02463-0. PMID 25225024.
  23. ^ Goldstein I, Kim NN, Clayton AH, DeRogatis LR, Giraldi A, Parish SJ, et al. (January 2017). "Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review". Mayo Clinic Proceedings. 92 (1): 114–128. doi:10.1016/j.mayocp.2016.09.018. PMID 27916394.
  24. ^ Sontheimer DL, Ables AZ (March 2001). "Is imipramine or buspirone treatment effective in patients wishing to discontinue long-term benzodiazepine use?". The Journal of Family Practice. 50 (3): 203. PMID 11252203.
  25. ^ Garrett AR, Hawley JS (April 2018). "SSRI-associated bruxism: A systematic review of published case reports". Neurology. Clinical Practice. 8 (2): 135–141. doi:10.1212/CPJ.0000000000000433. PMC 5914744. PMID 29708207.
  26. ^ Prisco V, Iannaccone T, Di Grezia G (1 April 2017). "Use of buspirone in selective serotonin reuptake inhibitor-induced sleep bruxism". European Psychiatry. Abstract of the 25th European Congress of Psychiatry. 41: S855. doi:10.1016/j.eurpsy.2017.01.1701. S2CID 148816505.
  27. ^ a b c "Buspirone monograph". Drugs.com. Retrieved 27 August 2011.
  28. ^ Geddes J, Gelder MG, Mayou R (2005). Psychiatry. Oxford [Oxfordshire]: Oxford University Press. p. 237. ISBN 978-0-19-852863-0.
  29. ^ Rissardo JP, Caprara AL (2020). "Buspirone-associated Movement Disorder: A Literature Review". Prague Medical Report. 121 (1): 5–24. doi:10.14712/23362936.2020.1. PMID 32191616. S2CID 213191429.
  30. ^ Fulton B, Brogden RN (1997). "Buspirone". CNS Drugs. 7 (1): 68–88. doi:10.2165/00023210-199707010-00007. ISSN 1172-7047.
  31. ^ a b c Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 886–. ISBN 978-0-7817-2845-4.
  32. ^ Lilja JJ, Kivistö KT, Backman JT, Lamberg TS, Neuvonen PJ (December 1998). "Grapefruit juice substantially increases plasma concentrations of buspirone". Clinical Pharmacology and Therapeutics. 64 (6): 655–660. doi:10.1016/S0009-9236(98)90056-X. PMID 9871430. S2CID 22009095.
  33. ^ Lamberg TS, Kivistö KT, Laitila J, Mårtensson K, Neuvonen PJ (1998). "The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone". European Journal of Clinical Pharmacology. 54 (9–10): 761–766. doi:10.1007/s002280050548. PMID 9923581. S2CID 21939719.
  34. ^ a b c Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  35. ^ Boess FG, Martin IL (1994). "Molecular biology of 5-HT receptors". Neuropharmacology. 33 (3–4): 275–317. doi:10.1016/0028-3908(94)90059-0. PMID 7984267. S2CID 35553281.
  36. ^ a b c d e f g h i j k l m Hamik A, Oksenberg D, Fischette C, Peroutka SJ (July 1990). "Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites". Biological Psychiatry. 28 (2): 99–109. doi:10.1016/0006-3223(90)90627-e. PMID 1974152. S2CID 25608914.
  37. ^ Peroutka SJ, Switzer JA, Hamik A (1989). "Identification of 5-hydroxytryptamine1D binding sites in human brain membranes". Synapse. 3 (1): 61–66. doi:10.1002/syn.890030109. PMID 2521959. S2CID 23503235.
  38. ^ Waeber C, Schoeffter P, Palacios JM, Hoyer D (June 1988). "Molecular pharmacology of 5-HT1D recognition sites: radioligand binding studies in human, pig and calf brain membranes". Naunyn-Schmiedeberg's Archives of Pharmacology. 337 (6): 595–601. doi:10.1007/bf00175783. PMID 2975354. S2CID 21344978.
  39. ^ a b c d e Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, et al. (1997). "RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist". Neuropharmacology. 36 (4–5): 621–629. doi:10.1016/s0028-3908(97)00049-x. PMID 9225287. S2CID 24930608.
  40. ^ Nelson DR, Thomas DR (May 1989). "[3H]-BRL 43694 (Granisetron), a specific ligand for 5-HT3 binding sites in rat brain cortical membranes". Biochemical Pharmacology. 38 (10): 1693–1695. doi:10.1016/0006-2952(89)90319-5. PMID 2543418.
  41. ^ a b Borsini F, Giraldo E, Monferini E, Antonini G, Parenti M, Bietti G, Donetti A (September 1995). "BIMT 17, a 5-HT2A receptor antagonist and 5-HT1A receptor full agonist in rat cerebral cortex". Naunyn-Schmiedeberg's Archives of Pharmacology. 352 (3): 276–282. doi:10.1007/bf00168557. PMID 8584042. S2CID 19340842.
  42. ^ Plassat JL, Amlaiky N, Hen R (August 1993). "Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase". Molecular Pharmacology. 44 (2): 229–236. PMID 8394987.
  43. ^ Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, et al. (September 1993). "A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms". Neuron. 11 (3): 449–458. doi:10.1016/0896-6273(93)90149-l. PMID 8398139. S2CID 28729004.
  44. ^ Ruat M, Traiffort E, Leurs R, Tardivel-Lacombe J, Diaz J, Arrang JM, Schwartz JC (September 1993). "Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation". Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8547–8551. Bibcode:1993PNAS...90.8547R. doi:10.1073/pnas.90.18.8547. PMC 47394. PMID 8397408.
  45. ^ Perry CK, Casey AB, Felsing DE, Vemula R, Zaka M, Herrington NB, et al. (February 2020). "Synthesis of novel 5-substituted-2-aminotetralin analogs: 5-HT1A and 5-HT7 G protein-coupled receptor affinity, 3D-QSAR and molecular modeling". Bioorganic & Medicinal Chemistry. 28 (3): 115262. doi:10.1016/j.bmc.2019.115262. PMID 31882369. S2CID 209498915.
  46. ^ a b Blier P, Curet O, Chaput Y, de Montigny C (July 1991). "Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission". Neuropharmacology. 30 (7): 691–701. doi:10.1016/0028-3908(91)90176-c. PMID 1681447. S2CID 44297577.
  47. ^ a b c d Bergman J, Roof RA, Furman CA, Conroy JL, Mello NK, Sibley DR, Skolnick P (March 2013). "Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors". The International Journal of Neuropsychopharmacology. 16 (2): 445–458. doi:10.1017/S1461145712000661. PMC 5100812. PMID 22827916.
  48. ^ a b c Tunnicliff G (September 1991). "Molecular basis of buspirone's anxiolytic action". Pharmacology & Toxicology. 69 (3): 149–156. doi:10.1111/j.1600-0773.1991.tb01289.x. PMID 1796057.
  49. ^ Zuideveld KP, Rusiç-Pavletiç J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M (December 2002). "Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats". The Journal of Pharmacology and Experimental Therapeutics. 303 (3): 1130–1137. doi:10.1124/jpet.102.036798. PMID 12438536. S2CID 14139919.
  50. ^ a b c Fava M (2007). "The combination of buspirone and bupropion in the treatment of depression". Psychotherapy and Psychosomatics. 76 (5): 311–312. doi:10.1159/000104708. PMID 17700052. S2CID 46284917.
  51. ^ a b Stern TA, Fava M, Wilens TE, Rosenbaum JF (27 April 2015). Massachusetts General Hospital Psychopharmacology and Neurotherapeutics E-Book. Elsevier Health Sciences. pp. 29–. ISBN 978-0-323-41323-7.
  52. ^ Nutt DJ, Ballenger JC (15 April 2008). Anxiety Disorders. John Wiley & Sons. pp. 395–. ISBN 978-0-470-98683-7.
  53. ^ Zhu Y, Chen G, Zhang K, Chen C, Chen W, Zhu M, Jiang H (November 2022). "High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach". Molecules. 27 (22): 8058. doi:10.3390/molecules27228058. PMC 9693510. PMID 36432161.
  54. ^ Zhu Y, Chen G, Zhang K, Chen C, Chen W, Zhu M, Jiang H (November 2022). "High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach". Molecules. 27 (22): 8058. doi:10.3390/molecules27228058. PMC 9693510. PMID 36432161.
  55. ^ Dockens RC, Salazar DE, Fulmor IE, Wehling M, Arnold ME, Croop R (November 2006). "Pharmacokinetics of a newly identified active metabolite of buspirone after administration of buspirone over its therapeutic dose range". Journal of Clinical Pharmacology. 46 (11): 1308–1312. doi:10.1177/0091270006292250. PMID 17050795. S2CID 25050964.
  56. ^ Jajoo HK, Mayol RF, LaBudde JA, Blair IA (1989). "Metabolism of the antianxiety drug buspirone in human subjects". Drug Metabolism and Disposition. 17 (6): 634–640. PMID 2575499.
  57. ^ Taylor DP, Moon SL (July 1991). "Buspirone and related compounds as alternative anxiolytics". Neuropeptides. 19 (Suppl): 15–19. doi:10.1016/0143-4179(91)90078-w. PMID 1679210. S2CID 13730683.
  58. ^ Yevich JP, Temple DL, New JS, Taylor DP, Riblet LA (February 1983). "Buspirone analogues. 1. Structure-activity relationships in a series of N-aryl- and heteroarylpiperazine derivatives". Journal of Medicinal Chemistry. 26 (2): 194–203. doi:10.1021/jm00356a014. PMID 6131130. S2CID 28619843.
  59. ^ Cybulski J, Chilmonczyk Z, Szelejewski W, Wojtasiewicz K, Wróbel JT (1992). "An Efficient Synthesis of Buspirone and its Analogues". Archiv der Pharmazie. 325 (5): 313–315. doi:10.1002/ardp.19923250513. S2CID 83676454.
  60. ^ Kuo DL (1993). "Pd(0)-catalysed Synthesis of Buspirone and Gepirone". Heterocycles. 36 (7): 1463–1469. doi:10.3987/COM-93-6357.
  61. ^ Mou J, Zong ZM, Wei XY (August 2008). "Facile Synthesis of Anxiolytic Buspirone". Organic Preparations and Procedures International. 40 (4): 391–394. doi:10.1080/00304940809458099. eISSN 1945-5453. ISSN 0030-4948. S2CID 95124245.
  62. ^ a b Allen LE, Ferguson HC, Kissel JW (May 1972). "Psychosedative agents. 2. 8-(4-Substituted 1-piperazinylalkyl)-8-azaspiro(4.5)decane-7,9-diones". Journal of Medicinal Chemistry. 15 (5): 477–479. doi:10.1021/jm00275a009. PMID 5035267.
  63. ^ DE2057845 idem Y Wu, J Rayburn, U.S. Patent 3,717,634 (1973 to Mead Johnson & Co).
  64. ^ US 3907801, Wu YH, Rayburn JW, issued 1975, assigned to Mead Johnson & Co 
  65. ^ US 3976776, Wu YH, Rayburn JW, issued 1976, assigned to Mead Johnson & Company 
  66. ^ US 4810789, Behme RJ, Kensler TT, Mikolasek DG, issued 1989, assigned to Bristol Myers Co 
  67. ^ US 4182763, Casten GP, McKinney GR, Newton RE, Tompkins EC, Weikel Jr JH, "Buspirone anti-anxiety method", published 1980-01-08, assigned to Mead Johnson & Co. and Bristol-Meyers Co. 
  68. ^ US 3907801, Hua WY, Warren RJ, "N-[(4-pyridyl-piperazino)-alkyl]-azaspiroalkanediones", published 1975-09-23, assigned to Mead Johnson & Co. 
  69. ^ "Approval Type-1 New Molecular Entry" (PDF). United States Federal Drug Administration. 9 September 1986.
  70. ^ a b Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 149–. ISBN 978-3-88763-075-1.
  71. ^ Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 57–. ISBN 978-94-011-4439-1.
  72. ^ a b "Buspirone". Drugs.com.
  73. ^ "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov. Retrieved 20 September 2019.
  74. ^ "Determination That BUSPAR (Buspirone Hydrochloride) Tablets, 10 Milligrams, 15 Milligrams, and 30 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness". Federal Register. 19 October 2010. Retrieved 20 September 2019.
  75. ^ Rabin RC (1 February 2019). "Shortage of Anxiety Drug Leaves Patients Scrambling". The New York Times. ISSN 0362-4331. Retrieved 20 September 2019.

External links

  •   Media related to Buspirone at Wikimedia Commons
  • "Buspirone". Drug Information Portal. U.S. National Library of Medicine.

January 26, 2023
buspirone, confused, with, bupropion, sold, under, brand, name, buspar, among, others, medication, primarily, used, treat, anxiety, disorders, particularly, generalized, anxiety, disorder, benefits, support, short, term, taken, mouth, take, four, weeks, have, . Not to be confused with Bupropion Buspirone sold under the brand name Buspar among others is a medication primarily used to treat anxiety disorders particularly generalized anxiety disorder 9 10 Benefits support its short term use 11 It is taken by mouth and it may take up to four weeks to have an effect 9 10 BuspironeClinical dataPronunciation ˈ b juː s p ɪ r oʊ n BEW spi rohn Trade namesBuspar NamanspinOther namesMJ 9022 1 1 AHFS Drugs comMonographMedlinePlusa688005PregnancycategoryAU B1Routes ofadministrationBy mouthATC codeN05BE01 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US onlyPharmacokinetic dataBioavailability3 9 2 Protein binding86 95 3 MetabolismLiver via CYP3A4 7 8 Metabolites5 OH Buspirone 6 OH Buspirone 8 OH Buspirone 1 PP 4 5 6 Elimination half life2 5 hours 7 ExcretionUrine 29 63 3 Feces 18 38 3 IdentifiersIUPAC name 8 4 4 Pyrimidin 2 yl piperazin 1 yl butyl 8 azaspiro 4 5 decane 7 9 dioneCAS Number36505 84 7 Y 33386 08 2 hydrochloride PubChem CID2477IUPHAR BPS36DrugBankDB00490 YChemSpider2383 YUNIITK65WKS8HLKEGGD07593 YChEBICHEBI 3223 YChEMBLChEMBL49 YCompTox Dashboard EPA DTXSID2022707ECHA InfoCard100 048 232Chemical and physical dataFormulaC 21H 31N 5O 2Molar mass385 512 g mol 13D model JSmol Interactive imageSMILES O C1CC2 CCCC2 CC O N1CCCCN1CCN c2ncccn2 CC1InChI InChI 1S C21H31N5O2 c27 18 16 21 6 1 2 7 21 17 19 28 26 18 11 4 3 10 24 12 14 25 15 13 24 20 22 8 5 9 23 20 h5 8 9H 1 4 6 7 10 17H2 YKey QWCRAEMEVRGPNT UHFFFAOYSA N Y verify Common side effects of buspirone include nausea headaches dizziness and difficulty concentrating 9 11 Serious side effects may include hallucinations serotonin syndrome and seizures 11 Its use in pregnancy appears to be safe but has not been well studied while use during breastfeeding has not been well studied 11 12 It is a serotonin 5 HT1A receptor agonist 2 Buspirone was first made in 1968 and approved for medical use in the United States in 1986 9 10 It is available as a generic medication 11 In 2020 it was the 55th most commonly prescribed medication in the United States with more than 12 million prescriptions 13 14 Contents 1 Medical uses 1 1 Anxiety 1 2 Other uses 1 2 1 Sexual dysfunction 1 2 2 Miscellaneous 2 Contraindications 3 Side effects 4 Overdose 5 Interactions 6 Pharmacology 6 1 Pharmacodynamics 6 2 Pharmacokinetics 7 Chemistry 7 1 Analogues 8 Synthesis 9 History 10 Society and culture 10 1 Generic names 10 2 Brand name 10 3 2019 shortage 11 Research 12 References 13 External linksMedical uses EditAnxiety Edit Buspirone is used for the short term and long term treatment of anxiety disorders or symptoms of anxiety 15 16 17 18 19 It is generally preferred over benzodiazepines because it does not activate the receptors that make drugs like alprazolam addictive 10 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 20 The drug has been shown to be similarly effective in the treatment of generalized anxiety disorder GAD to benzodiazepines including diazepam alprazolam lorazepam and clorazepate 2 Buspirone is not known to be effective in the treatment of other anxiety disorders besides GAD 21 although there is some limited evidence that it may be useful in the treatment of social phobia as an adjunct to selective serotonin reuptake inhibitors SSRIs 2 22 Other uses Edit Sexual dysfunction Edit There is some evidence that buspirone on its own may be useful in the treatment of hypoactive sexual desire disorder HSDD in women 23 Miscellaneous Edit Buspirone is not effective as a treatment for benzodiazepine withdrawal barbiturate withdrawal or alcohol withdrawal delirium tremens 24 SSRI and SNRI antidepressants such as paroxetine and venlafaxine may cause jaw pain jaw spasm reversible syndrome although it is not common and buspirone appears to be successful in treating bruxism on SSRI SNRI induced jaw clenching 25 26 Contraindications EditBuspirone has these contraindications 27 28 Hypersensitivity to buspirone Metabolic acidosis as in diabetes Should not be used with MAO inhibitors Severely compromised liver and or kidney functionSide effects EditMain article List of side effects of buspirone Known side effects associated with buspirone include dizziness headaches nausea tinnitus and paresthesia 2 Buspirone is relatively well tolerated and is not associated with sedation cognitive and psychomotor impairment muscle relaxation physical dependence or anticonvulsant effects 2 In addition buspirone does not produce euphoria 20 and is not a drug of abuse 16 Dyskinesia akathisia myoclonus parkinsonism and dystonia were reported associated with buspirone 29 It is unclear if there is a risk of tardive dyskinesia or other movement disorders with buspirone 9 Overdose EditBuspirone appears to be relatively benign in cases of single drug overdose although no definitive data on this subject appear to be available 30 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 15 16 18 In early clinical trials buspirone was given at dosages even as high as 2 400 mg day with akathisia tremor and muscle rigidity observed 31 Deliberate overdoses with 250 mg and up to 300 mg buspirone have resulted in drowsiness in about 50 of individuals 31 One death has been reported in a co ingestion of 450 mg buspirone with alprazolam diltiazem alcohol cocaine 31 Interactions EditBuspirone has been shown in vitro to be metabolized by the enzyme CYP3A4 8 This finding is consistent with the in vivo interactions observed between buspirone and these inhibitors or inducers of cytochrome P450 3A4 CYP3A4 among others 27 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 32 See grapefruit drug interactions Fluvoxamine Moderately increase plasma levels of buspirone 33 Elevated blood pressure has been reported when buspirone has been administered to patients taking monoamine oxidase inhibitors MAOIs 27 Pharmacology EditPharmacodynamics Edit Buspirone 34 Site Ki nM Species Ref5 HT1A 3 98 21421 median Human 34 35 5 HT1B gt 100 000 Rat 36 5 HT1D 22 000 42 700 Human 37 38 5 HT2A 138759 1 300 HumanRat 39 36 39 5 HT2B 214 Human 39 5 HT2C 4901 100 6 026 HumanRat pig 39 36 39 5 HT3 gt 10 000 Rat 40 41 5 HT4 gt 10 000 Rat 41 5 HT6 398 Mouse 42 5 HT7 375 381840 RatHuman 43 44 45 a1 1 000 Rat 36 a2 6 000 Rat 46 a2A 7 3 1 PP Human 36 b 8 800 Rat 36 D1 33 000 Rat 36 D2 484240 HumanRat 47 36 D3 98 Human 47 D4 29 Human 47 mACh 38 000 Rat 36 GABAA BDZ gt 100 000 Rat 36 Values are Ki nM The smaller the value the more strongly the drug binds to the site Buspirone acts as an agonist of the serotonin 5 HT1A receptor with high affinity 2 36 It is a partial agonist of both presynaptic 5 HT1A receptors which are inhibitory autoreceptors and postsynaptic 5 HT1A receptors 2 It is thought that the main effects of buspirone are mediated via its interaction with the presynaptic 5 HT1A receptor thus reducing the firing of serotonin producing neurons 2 Buspirone also has lower affinities for the serotonin 5 HT2A 5 HT2B 5 HT2C 5 HT6 and 5 HT7 receptors 34 In addition to binding to serotonin receptors buspirone is an antagonist of the dopamine D2 receptor with weak affinity 2 36 It preferentially blocks inhibitory presynaptic D2 autoreceptors and antagonizes postsynaptic D2 receptors only at higher doses 2 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 2 Buspirone has also been found to bind with much higher affinity to the dopamine D3 and D4 receptors where it is similarly an antagonist 47 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 a2 adrenergic receptor antagonist 46 48 49 This metabolite may be responsible for the increased noradrenergic and dopaminergic activity observed with buspirone in animals 48 50 In addition 1 PP may play an important role in the antidepressant effects of buspirone 50 Buspirone also has very weak and probably clinically unimportant affinity for the a1 adrenergic receptor 36 51 However buspirone has been reported to have shown significant and selective intrinsic efficacy at the a1 adrenergic receptor expressed in a tissue and species dependent manner 51 Unlike benzodiazepines buspirone does not interact with the GABAA receptor complex 2 52 Pharmacokinetics Edit Buspirone has a low oral bioavailability of 3 9 relative to intravenous injection due to extensive first pass metabolism 2 The time to peak plasma levels following ingestion is 0 9 to 1 5 hours 2 It is reported to have an elimination half life of 2 8 hours 2 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 4 Buspirone is metabolized primarily by CYP3A4 and prominent drug interactions with inhibitors and inducers of this enzyme have been observed 7 8 Major metabolites of buspirone include 5 hydroxybuspirone 6 hydroxybuspirone 8 hydroxybuspirone and 1 PP 53 4 5 6 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 5 The metabolite is a high affinity partial agonist of the 5 HT1A receptor Ki 25 nM similarly to buspirone and has demonstrated occupancy of the 5 HT1A receptor in vivo 5 As such it is likely to play an important role in the therapeutic effects of buspirone 5 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 48 50 Phase I Metabolism of buspirone in humans 54 55 56 8 Chemistry EditBuspirone is a member of the azapirone chemical class and consists of azaspirodecanedione and pyrimidinylpiperazine components linked together by a butyl chain Analogues Edit Structural analogues of buspirone include other azapirones like gepirone ipsapirone perospirone and tandospirone 57 A number of analogues are recorded 58 Synthesis EditA number of more modern methods of synthesis have also been reported list not exhaustive 59 60 61 Synthesis 62 Patents 63 64 65 Polymorphic crystalline form 66 Alkylation of 1 2 pyrimidyl piperazine 20980 22 7 1 with 3 chloro 1 cyanopropane 4 chlorobutyronitrile 628 20 6 2 gives 33386 14 0 3 the reduction of the nitrile group is performed either by catalytic hydrogenation or with LAH giving 33386 20 8 4 The primary amine is then reacted with 3 3 tetramethyleneglutaric anhydride 5662 95 3 5 in order to yield Buspirone 6 History EditBuspirone was first synthesized by a team at Mead Johnson in 1968 21 but was not patented until 1980 67 62 68 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 2 In 1986 Bristol Myers Squibb gained FDA approval for buspirone in the treatment of GAD 21 69 The patent expired in 2001 and buspirone is now available as a generic drug Society and culture Edit Buspar buspirone 10 mg tablets Generic names Edit Buspirone is the INN BAN DCF and DCIT of buspirone while buspirone hydrochloride is its USAN BANM and JAN 1 70 71 72 Brand name Edit Buspirone was primarily sold under the brand name Buspar 70 72 Buspar is currently listed as discontinued by the US Federal Drug Administration 73 In 2010 in response to a citizen petition the US FDA determined that Buspar was not withdrawn from sale for reasons of safety or effectiveness 74 2019 shortage Edit Due to interrupted production at a Mylan Pharmaceuticals plant in Morgantown West Virginia the United States experienced a shortage of buspirone in 2019 75 Research EditSome tentative research supports other uses such as the treatment of depression and behavioral problems following brain damage 2 References Edit a b Elks J 14 November 2014 The Dictionary of Drugs Chemical Data Chemical Data Structures and Bibliographies Springer pp 192 ISBN 978 1 4757 2085 3 a b c d e f g h i j k l m n o p q r Loane C Politis M June 2012 Buspirone what is it all about Brain Research 1461 111 118 doi 10 1016 j brainres 2012 04 032 PMID 22608068 S2CID 11734819 a b c buspirone Rx BuSpar Buspirex more Medscape Reference WebMD Retrieved 14 November 2013 a b c Gammans RE Mayol RF LaBudde JA March 1986 Metabolism and disposition of buspirone The American Journal of Medicine 80 3B 41 51 doi 10 1016 0002 9343 86 90331 1 PMID 3515929 a b c d e Schatzberg AF Nemeroff CB 2009 The American Psychiatric Publishing Textbook of Psychopharmacology American Psychiatric Pub pp 490 ISBN 978 1 58562 309 9 a b Wong H Dockens RC Pajor L Yeola S Grace JE Stark AD et al August 2007 6 Hydroxybuspirone is a major active metabolite of buspirone assessment of pharmacokinetics and 5 hydroxytryptamine1A receptor occupancy in rats Drug Metabolism and Disposition 35 8 1387 1392 doi 10 1124 dmd 107 015768 PMID 17494642 S2CID 25558546 a b c Mahmood I Sahajwalla C April 1999 Clinical pharmacokinetics and pharmacodynamics of buspirone an anxiolytic drug Clinical Pharmacokinetics 36 4 277 287 doi 10 2165 00003088 199936040 00003 PMID 10320950 S2CID 1102318 a b c d Zhu M Zhao W Jimenez H Zhang D Yeola S Dai R et al April 2005 Cytochrome P450 3A mediated metabolism of buspirone in human liver microsomes Drug Metabolism and Disposition 33 4 500 507 doi 10 1124 dmd 104 000836 PMID 15640381 S2CID 10142905 a b c d e Buspirone Hydrochloride Monograph for Professionals Drugs com American Society of Health System Pharmacists Retrieved 3 March 2019 a b c d Wilson TK Tripp J January 2018 Buspirone StatPearls PMID 30285372 a b c d e British national formulary BNF 76 76 ed Pharmaceutical Press 2018 p 338 ISBN 9780857113382 Buspirone Pregnancy and Breastfeeding Warnings Drugs com Retrieved 3 March 2019 The Top 300 of 2020 ClinCalc Retrieved 7 October 2022 Buspirone Drug Usage Statistics ClinCalc Retrieved 7 October 2022 a b BUSPIRONE HCL buspirone hydrochloride tablet Watson Laboratories Inc DailyMed Watson Laboratories Inc July 2013 Retrieved 14 November 2013 a b c BUSPAR buspirone hydrochloride Tablets 5 mg amp 10 mg PRODUCT INFORMATION PDF TGA eBusiness Services Aspen Pharma Pty Ltd January 2010 Retrieved 14 November 2013 Rossi S ed 2013 Australian Medicines Handbook 2013 ed Adelaide The Australian Medicines Handbook Unit Trust ISBN 978 0 9805790 9 3 a b Buspirone 10mg Tablets electronic Medicines Compendium Actavis UK Ltd 10 September 2012 Retrieved 14 November 2013 Joint Formulary Committee British National Formulary BNF Pharmaceutical Press p 224 a b Sadock BJ Sadock VA Ruiz P 22 September 2014 Kaplan and Sadock s Synopsis of Psychiatry Behavioral Sciences Clinical Psychiatry Wolters Kluwer Health pp 3211 ISBN 978 1 4698 8375 5 a b c Howland RH November 2015 Buspirone Back to the Future Journal of Psychosocial Nursing and Mental Health Services 53 11 21 24 doi 10 3928 02793695 20151022 01 PMID 26535760 Masdrakis VG Turic D Baldwin DS 2013 Pharmacological treatment of social anxiety disorder Anxiety Disorders Modern Trends in Pharmacopsychiatry Vol 29 pp 144 53 doi 10 1159 000351960 ISBN 978 3 318 02463 0 PMID 25225024 Goldstein I Kim NN Clayton AH DeRogatis LR Giraldi A Parish SJ et al January 2017 Hypoactive Sexual Desire Disorder International Society for the Study of Women s Sexual Health ISSWSH Expert Consensus Panel Review Mayo Clinic Proceedings 92 1 114 128 doi 10 1016 j mayocp 2016 09 018 PMID 27916394 Sontheimer DL Ables AZ March 2001 Is imipramine or buspirone treatment effective in patients wishing to discontinue long term benzodiazepine use The Journal of Family Practice 50 3 203 PMID 11252203 Garrett AR Hawley JS April 2018 SSRI associated bruxism A systematic review of published case reports Neurology Clinical Practice 8 2 135 141 doi 10 1212 CPJ 0000000000000433 PMC 5914744 PMID 29708207 Prisco V Iannaccone T Di Grezia G 1 April 2017 Use of buspirone in selective serotonin reuptake inhibitor induced sleep bruxism European Psychiatry Abstract of the 25th European Congress of Psychiatry 41 S855 doi 10 1016 j eurpsy 2017 01 1701 S2CID 148816505 a b c Buspirone monograph Drugs com Retrieved 27 August 2011 Geddes J Gelder MG Mayou R 2005 Psychiatry Oxford Oxfordshire Oxford University Press p 237 ISBN 978 0 19 852863 0 Rissardo JP Caprara AL 2020 Buspirone associated Movement Disorder A Literature Review Prague Medical Report 121 1 5 24 doi 10 14712 23362936 2020 1 PMID 32191616 S2CID 213191429 Fulton B Brogden RN 1997 Buspirone CNS Drugs 7 1 68 88 doi 10 2165 00023210 199707010 00007 ISSN 1172 7047 a b c Dart RC 2004 Medical Toxicology Lippincott Williams amp Wilkins pp 886 ISBN 978 0 7817 2845 4 Lilja JJ Kivisto KT Backman JT Lamberg TS Neuvonen PJ December 1998 Grapefruit juice substantially increases plasma concentrations of buspirone Clinical Pharmacology and Therapeutics 64 6 655 660 doi 10 1016 S0009 9236 98 90056 X PMID 9871430 S2CID 22009095 Lamberg TS Kivisto KT Laitila J Martensson K Neuvonen PJ 1998 The effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of buspirone European Journal of Clinical Pharmacology 54 9 10 761 766 doi 10 1007 s002280050548 PMID 9923581 S2CID 21939719 a b c Roth BL Driscol J PDSP Ki Database Psychoactive Drug Screening Program PDSP University of North Carolina at Chapel Hill and the United States National Institute of Mental Health Retrieved 14 August 2017 Boess FG Martin IL 1994 Molecular biology of 5 HT receptors Neuropharmacology 33 3 4 275 317 doi 10 1016 0028 3908 94 90059 0 PMID 7984267 S2CID 35553281 a b c d e f g h i j k l m Hamik A Oksenberg D Fischette C Peroutka SJ July 1990 Analysis of tandospirone SM 3997 interactions with neurotransmitter receptor binding sites Biological Psychiatry 28 2 99 109 doi 10 1016 0006 3223 90 90627 e PMID 1974152 S2CID 25608914 Peroutka SJ Switzer JA Hamik A 1989 Identification of 5 hydroxytryptamine1D binding sites in human brain membranes Synapse 3 1 61 66 doi 10 1002 syn 890030109 PMID 2521959 S2CID 23503235 Waeber C Schoeffter P Palacios JM Hoyer D June 1988 Molecular pharmacology of 5 HT1D recognition sites radioligand binding studies in human pig and calf brain membranes Naunyn Schmiedeberg s Archives of Pharmacology 337 6 595 601 doi 10 1007 bf00175783 PMID 2975354 S2CID 21344978 a b c d e Bonhaus DW Weinhardt KK Taylor M DeSouza A McNeeley PM Szczepanski K et al 1997 RS 102221 a novel high affinity and selective 5 HT2C receptor antagonist Neuropharmacology 36 4 5 621 629 doi 10 1016 s0028 3908 97 00049 x PMID 9225287 S2CID 24930608 Nelson DR Thomas DR May 1989 3H BRL 43694 Granisetron a specific ligand for 5 HT3 binding sites in rat brain cortical membranes Biochemical Pharmacology 38 10 1693 1695 doi 10 1016 0006 2952 89 90319 5 PMID 2543418 a b Borsini F Giraldo E Monferini E Antonini G Parenti M Bietti G Donetti A September 1995 BIMT 17 a 5 HT2A receptor antagonist and 5 HT1A receptor full agonist in rat cerebral cortex Naunyn Schmiedeberg s Archives of Pharmacology 352 3 276 282 doi 10 1007 bf00168557 PMID 8584042 S2CID 19340842 Plassat JL Amlaiky N Hen R August 1993 Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase Molecular Pharmacology 44 2 229 236 PMID 8394987 Lovenberg TW Baron BM de Lecea L Miller JD Prosser RA Rea MA et al September 1993 A novel adenylyl cyclase activating serotonin receptor 5 HT7 implicated in the regulation of mammalian circadian rhythms Neuron 11 3 449 458 doi 10 1016 0896 6273 93 90149 l PMID 8398139 S2CID 28729004 Ruat M Traiffort E Leurs R Tardivel Lacombe J Diaz J Arrang JM Schwartz JC September 1993 Molecular cloning characterization and localization of a high affinity serotonin receptor 5 HT7 activating cAMP formation Proceedings of the National Academy of Sciences of the United States of America 90 18 8547 8551 Bibcode 1993PNAS 90 8547R doi 10 1073 pnas 90 18 8547 PMC 47394 PMID 8397408 Perry CK Casey AB Felsing DE Vemula R Zaka M Herrington NB et al February 2020 Synthesis of novel 5 substituted 2 aminotetralin analogs 5 HT1A and 5 HT7 G protein coupled receptor affinity 3D QSAR and molecular modeling Bioorganic amp Medicinal Chemistry 28 3 115262 doi 10 1016 j bmc 2019 115262 PMID 31882369 S2CID 209498915 a b Blier P Curet O Chaput Y de Montigny C July 1991 Tandospirone and its metabolite 1 2 pyrimidinyl piperazine II Effects of acute administration of 1 PP and long term administration of tandospirone on noradrenergic neurotransmission Neuropharmacology 30 7 691 701 doi 10 1016 0028 3908 91 90176 c PMID 1681447 S2CID 44297577 a b c d Bergman J Roof RA Furman CA Conroy JL Mello NK Sibley DR Skolnick P March 2013 Modification of cocaine self administration by buspirone buspar potential involvement of D3 and D4 dopamine receptors The International Journal of Neuropsychopharmacology 16 2 445 458 doi 10 1017 S1461145712000661 PMC 5100812 PMID 22827916 a b c Tunnicliff G September 1991 Molecular basis of buspirone s anxiolytic action Pharmacology amp Toxicology 69 3 149 156 doi 10 1111 j 1600 0773 1991 tb01289 x PMID 1796057 Zuideveld KP Rusic Pavletic J Maas HJ Peletier LA Van der Graaf PH Danhof M December 2002 Pharmacokinetic pharmacodynamic modeling of buspirone and its metabolite 1 2 pyrimidinyl piperazine in rats The Journal of Pharmacology and Experimental Therapeutics 303 3 1130 1137 doi 10 1124 jpet 102 036798 PMID 12438536 S2CID 14139919 a b c Fava M 2007 The combination of buspirone and bupropion in the treatment of depression Psychotherapy and Psychosomatics 76 5 311 312 doi 10 1159 000104708 PMID 17700052 S2CID 46284917 a b Stern TA Fava M Wilens TE Rosenbaum JF 27 April 2015 Massachusetts General Hospital Psychopharmacology and Neurotherapeutics E Book Elsevier Health Sciences pp 29 ISBN 978 0 323 41323 7 Nutt DJ Ballenger JC 15 April 2008 Anxiety Disorders John Wiley amp Sons pp 395 ISBN 978 0 470 98683 7 Zhu Y Chen G Zhang K Chen C Chen W Zhu M Jiang H November 2022 High Throughput Metabolic Soft Spot Identification in Liver Microsomes by LC UV MS Application of a Single Variable Incubation Time Approach Molecules 27 22 8058 doi 10 3390 molecules27228058 PMC 9693510 PMID 36432161 Zhu Y Chen G Zhang K Chen C Chen W Zhu M Jiang H November 2022 High Throughput Metabolic Soft Spot Identification in Liver Microsomes by LC UV MS Application of a Single Variable Incubation Time Approach Molecules 27 22 8058 doi 10 3390 molecules27228058 PMC 9693510 PMID 36432161 Dockens RC Salazar DE Fulmor IE Wehling M Arnold ME Croop R November 2006 Pharmacokinetics of a newly identified active metabolite of buspirone after administration of buspirone over its therapeutic dose range Journal of Clinical Pharmacology 46 11 1308 1312 doi 10 1177 0091270006292250 PMID 17050795 S2CID 25050964 Jajoo HK Mayol RF LaBudde JA Blair IA 1989 Metabolism of the antianxiety drug buspirone in human subjects Drug Metabolism and Disposition 17 6 634 640 PMID 2575499 Taylor DP Moon SL July 1991 Buspirone and related compounds as alternative anxiolytics Neuropeptides 19 Suppl 15 19 doi 10 1016 0143 4179 91 90078 w PMID 1679210 S2CID 13730683 Yevich JP Temple DL New JS Taylor DP Riblet LA February 1983 Buspirone analogues 1 Structure activity relationships in a series of N aryl and heteroarylpiperazine derivatives Journal of Medicinal Chemistry 26 2 194 203 doi 10 1021 jm00356a014 PMID 6131130 S2CID 28619843 Cybulski J Chilmonczyk Z Szelejewski W Wojtasiewicz K Wrobel JT 1992 An Efficient Synthesis of Buspirone and its Analogues Archiv der Pharmazie 325 5 313 315 doi 10 1002 ardp 19923250513 S2CID 83676454 Kuo DL 1993 Pd 0 catalysed Synthesis of Buspirone and Gepirone Heterocycles 36 7 1463 1469 doi 10 3987 COM 93 6357 Mou J Zong ZM Wei XY August 2008 Facile Synthesis of Anxiolytic Buspirone Organic Preparations and Procedures International 40 4 391 394 doi 10 1080 00304940809458099 eISSN 1945 5453 ISSN 0030 4948 S2CID 95124245 a b Allen LE Ferguson HC Kissel JW May 1972 Psychosedative agents 2 8 4 Substituted 1 piperazinylalkyl 8 azaspiro 4 5 decane 7 9 diones Journal of Medicinal Chemistry 15 5 477 479 doi 10 1021 jm00275a009 PMID 5035267 DE2057845 idem Y Wu J Rayburn U S Patent 3 717 634 1973 to Mead Johnson amp Co US 3907801 Wu YH Rayburn JW issued 1975 assigned to Mead Johnson amp Co US 3976776 Wu YH Rayburn JW issued 1976 assigned to Mead Johnson amp Company US 4810789 Behme RJ Kensler TT Mikolasek DG issued 1989 assigned to Bristol Myers Co US 4182763 Casten GP McKinney GR Newton RE Tompkins EC Weikel Jr JH Buspirone anti anxiety method published 1980 01 08 assigned to Mead Johnson amp Co and Bristol Meyers Co US 3907801 Hua WY Warren RJ N 4 pyridyl piperazino alkyl azaspiroalkanediones published 1975 09 23 assigned to Mead Johnson amp Co Approval Type 1 New Molecular Entry PDF United States Federal Drug Administration 9 September 1986 a b Index Nominum 2000 International Drug Directory Taylor amp Francis January 2000 pp 149 ISBN 978 3 88763 075 1 Morton IK Hall JM 6 December 2012 Concise Dictionary of Pharmacological Agents Properties and Synonyms Springer Science amp Business Media pp 57 ISBN 978 94 011 4439 1 a b Buspirone Drugs com Drugs FDA FDA Approved Drug Products www accessdata fda gov Retrieved 20 September 2019 Determination That BUSPAR Buspirone Hydrochloride Tablets 10 Milligrams 15 Milligrams and 30 Milligrams Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness Federal Register 19 October 2010 Retrieved 20 September 2019 Rabin RC 1 February 2019 Shortage of Anxiety Drug Leaves Patients Scrambling The New York Times ISSN 0362 4331 Retrieved 20 September 2019 External links Edit Media related to Buspirone at Wikimedia Commons Buspirone Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Buspirone amp oldid 1135358680, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.