Banner
Identification
Name Buspirone
Accession Number DB00490 (APRD00222)
Type small molecule
Groups approved
Description

An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Buspirona [INN-Spanish]
  • Buspirone
  • Buspirone HCL
  • Buspironum [INN-Latin]
Brand names
  • Ansial
  • Ansiced
  • Anxiron
  • Axoren
  • Bespar
  • Buspar
  • Buspimen
  • Buspinol
  • Buspisal
  • Censpar
  • Lucelan
  • Narol
  • Travin
  • Wellbutrin XL
Brand name mixtures Not Available
Categories
  • Anti-anxiety Agents
  • Serotonin Agonists
  • Anxiolytics sedatives and hypnotics
CAS number 36505-84-7
Weight Average: 385.5031
Monoisotopic: 385.247775261
Chemical Formula C21H31N5O2
InChI Key InChIKey=QWCRAEMEVRGPNT-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
8-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-8-azaspiro[4.5]decane-7,9-dione
SMILES
O=C1CC2(CCCC2)CC(=O)N1CCCCN1CCN(CC1)C1=NC=CC=N1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Delta Lactams
  • Azaspirodecanes
Substructures
  • Delta Lactams
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Piperazines
  • Pyrimidines and Derivatives
  • Piperidines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Carboxylic Acids and Derivatives
  • Azaspirodecanes
  • Cyanamides
Pharmacology
Indication For the management of anxiety disorders or the short-term relief of the symptoms of anxiety, and also as an augmention of SSRI-treatment against depression.
Pharmacodynamics Buspirone is used in the treatment of generalized anxiety where it has advantages over other antianxiety drugs because it does not cause sedation (drowsiness) and does not cause tolerance or physical dependence. Buspirone differs from typical benzodiazepine anxiolytics in that it does not exert anticonvulsant or muscle relaxant effects. It also lacks the prominent sedative effect that is associated with more typical anxiolytics. in vitro preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT1A) receptors. Buspirone has no significant affinity for benzodiazepine receptors and does not affect GABA binding in vitro or in vivo when tested in preclinical models. Buspirone has moderate affinity for brain D2-dopamine receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems.
Mechanism of action Buspirone binds to 5-HT type 1A serotonin receptors on presynaptic neurons in the dorsal raphe and on postsynaptic neurons in the hippocampus, thus inhibiting the firing rate of 5-HT-containing neurons in the dorsal raphe. Buspirone also binds at dopamine type 2 (DA2) receptors, blocking presynaptic dopamine receptors. Buspirone increases firing in the locus ceruleus, an area of brain where norepinephrine cell bodies are found in high concentration. The net result of buspirone actions is that serotonergic activity is suppressed while noradrenergic and dopaminergic cell firing is enhanced.
Absorption Rapidly absorbed in man. Bioavailability is low and variable (approximately 5%) due to extensive first pass metabolism.
Volume of distribution Not Available
Protein binding 95% (approximately 70% bound to albumin, 30% bound to alpha 1 -acid glycoprotein)
Metabolism

Metabolized hepatically, primarily by oxidation by cytochrome P450 3A4 producing several hydroxylated derivatives and a pharmacologically active metabolite, 1-pyrimidinylpiperazine (1-PP)

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A5 Buspirone N-oxide N-oxidation
Cytochrome P450 2D6 Buspirone N-oxide N-oxidation
Cytochrome P450 3A4 1-Pyrimidinylpiperazine N-dealkylation 8.7 0.74
Cytochrome P450 3A4 Buspirone N-oxide N-oxidation 34.0 1.64
Cytochrome P450 3A4 3′-Hydroxybuspirone Hydroxylation 4.3 0.30
Cytochrome P450 3A4 5-Hydroxybuspirone Hydroxylation 11.4 0.77
Cytochrome P450 3A4 5-Hydroxybuspirone Hydroxylation 514 7.5
Cytochrome P450 3A4 6'-Hydroxybuspirone Hydroxylation 8.8 1.37
Route of elimination In a single-dose study using 14C-labeled buspirone, 29% to 63% of the dose was excreted in the urine within 24 hours, primarily as metabolites; fecal excretion accounted for 18% to 38% of the dose.
Half life 2-3 hours (although the action of a single dose is much longer than the short halflife indicates).
Clearance Not Available
Toxicity Oral, rat LD50 = 136 mg/kg. Symptoms of overdose include dizziness, drowsiness, nausea or vomiting, severe stomach upset, and unusually small pupils.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co pharmaceutical research institute
  • Actavis totowa llc
  • Apotex inc
  • Dr reddys laboratories ltd
  • Egis pharmaceuticals
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Kv pharmaceutical co
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Wellbutrin xl 300 mg tablet 8.68 USD tablet
Wellbutrin xl 150 mg tablet 6.58 USD tablet
Buspar 30 mg tablet 5.52 USD tablet
Buspirone hcl powder 4.74 USD g
Buspirone hcl 30 mg tablet 3.71 USD tablet
Buspar 15 mg tablet 3.07 USD tablet
Buspirone hcl 15 mg tablet 2.16 USD tablet
Buspar 10 mg tablet 2.05 USD tablet
Buspirone hcl 7.5 mg tablet 1.62 USD tablet
Buspirone hcl 10 mg tablet 1.42 USD tablet
Buspar 5 mg tablet 1.18 USD tablet
Vanspar 7.5 mg tablet 1.18 USD tablet
Buspar 10 mg Tablet 1.12 USD tablet
Buspirone hcl 5 mg tablet 0.79 USD tablet
Apo-Buspirone 10 mg Tablet 0.62 USD tablet
Novo-Buspirone 10 mg Tablet 0.62 USD tablet
Nu-Buspirone 10 mg Tablet 0.62 USD tablet
Pms-Buspirone 10 mg Tablet 0.62 USD tablet
Ratio-Buspirone 10 mg Tablet 0.62 USD tablet
Patents Not Available
Properties
State solid
Melting point 201.5-202.5oC
Experimental Properties
Property Value Source
water solubility 21.4 mg/L PhysProp
logP 2.3 PhysProp
Predicted Properties
Property Value Source
water solubility 5.88e-01 g/l ALOGPS
logP 1.95 ALOGPS
logP 1.78 ChemAxon Molconvert
logS -2.82 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 69.64 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 108.89 ChemAxon Molconvert
polarizability 44.12 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06861 Link_out
PubChem Compound 2477 Link_out
PubChem Substance 46508113 Link_out
ChemSpider 2383 Link_out
ChEBI 3223 Link_out
ChEMBL 3223 Link_out
Therapeutic Targets Database DAP000031 Link_out
PharmGKB PA448689 Link_out
Drug Product Database 2242149 Link_out
RxList http://www.rxlist.com/cgi/generic/buspir.htm Link_out
Drugs.com http://www.drugs.com/buspirone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Buspirone Link_out
ATC Codes
  • N05BE01
AHFS Codes
  • 28:24.92
PDB Entries Not Available
FDA label show (274.5 KB)
MSDS show (75.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Always take at the same time with respect to meals.
  • Avoid alcohol.
  • Avoid taking grapefruit or grapefruit juice throughout treatment.
  • Take with food.
Targets

1. 5-hydroxytryptamine 1A receptor

Pharmacological action: yes
Actions: partial agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. de Boer SF, Lesourd M, Mocaer E, Koolhaas JM: Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine1A receptors: A comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, eltoprazine, and WAY-100635. J Pharmacol Exp Ther. 1999 Mar;288(3):1125-33. Pubmed
  2. Rehman J, Kaynan A, Christ G, Valcic M, Maayani S, Melman A: Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor. Brain Res. 1999 Mar 13;821(2):414-25. Pubmed
  3. Liang KC: Pre- or post-training injection of buspirone impaired retention in the inhibitory avoidance task: involvement of amygdala 5-HT1A receptors. Eur J Neurosci. 1999 May;11(5):1491-500. Pubmed
  4. Becker C, Hamon M, Benoliel JJ: Prevention by 5-HT1A receptor agonists of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat. Neuropharmacology. 1999 Apr;38(4):525-32. Pubmed
  5. Dupuis DS, Tardif S, Wurch T, Colpaert FC, Pauwels PJ: Modulation of 5-HT1A receptor signalling by point-mutation of cysteine351 in the rat Galpha(o) protein. Neuropharmacology. 1999 Jul;38(7):1035-41. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Osei-Owusu P, Scrogin KE: Buspirone raises blood pressure through activation of sympathetic nervous system and by direct activation of alpha1-adrenergic receptors after severe hemorrhage. J Pharmacol Exp Ther. 2004 Jun;309(3):1132-40. Epub 2004 Feb 9. Pubmed

2. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Malt EA, Olafsson S, Aakvaag A, Lund A, Ursin H: Altered dopamine D2 receptor function in fibromyalgia patients: a neuroendocrine study with buspirone in women with fibromyalgia compared to female population based controls. J Affect Disord. 2003 Jun;75(1):77-82. Pubmed
  2. Boido A, Boido CC, Sparatore F: Synthesis and pharmacological evaluation of aryl/heteroaryl piperazinyl alkyl benzotriazoles as ligands for some serotonin and dopamine receptor subtypes. Farmaco. 2001 Apr;56(4):263-75. Pubmed
  3. Nader MA, Hannemann M: Interactions of buspirone or gepirone with nicotine on schedule-controlled behavior of pigeons. Behav Pharmacol. 1993 Jun;4(3):263-268. Pubmed
  4. Pache DM, Fernandez-Perez S, Sewell RD: Buspirone differentially modifies short-term memory function in a combined delayed matching/non-matching to position task. Eur J Pharmacol. 2003 Sep 23;477(3):205-11. Pubmed
  5. Fernandez-Perez S, Pache DM, Sewell RD: Co-administration of fluoxetine and WAY100635 improves short-term memory function. Eur J Pharmacol. 2005 Oct 17;522(1-3):78-83. Epub 2005 Oct 7. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhu M, Zhao W, Jimenez H, Zhang D, Yeola S, Dai R, Vachharajani N, Mitroka J: Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7. Epub 2005 Jan 7. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhu M, Zhao W, Jimenez H, Zhang D, Yeola S, Dai R, Vachharajani N, Mitroka J: Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7. Epub 2005 Jan 7. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Zhu M, Zhao W, Jimenez H, Zhang D, Yeola S, Dai R, Vachharajani N, Mitroka J: Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7. Epub 2005 Jan 7. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 28, 2011 15:18

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.