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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:29:17 UTC
HMDB IDHMDB14633
Secondary Accession NumbersNone
Metabolite Identification
Common NameBuspirone
DescriptionBuspirone is only found in individuals that have used or taken this drug. It is 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]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.
Structure
Thumb
Synonyms
ValueSource
8-(4-(4-(2-Pyrimidinyl)-1-piperizinyl)butyl)-8-azaspiro(4,5)decane-7,9-dioneChEBI
BuspironaChEBI
BuspironumChEBI
Chemical FormulaC21H31N5O2
Average Molecular Weight385.5031
Monoisotopic Molecular Weight385.247775261
IUPAC Name8-{4-[4-(pyrimidin-2-yl)piperazin-1-yl]butyl}-8-azaspiro[4.5]decane-7,9-dione
Traditional Namebuspirone
CAS Registry Number36505-84-7
SMILES
O=C1CC2(CCCC2)CC(=O)N1CCCCN1CCN(CC1)C1=NC=CC=N1
InChI Identifier
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
InChI KeyInChIKey=QWCRAEMEVRGPNT-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentN-arylpiperazines
Alternative Parents
Substituents
  • N-arylpiperazine
  • Azaspirodecanedione
  • Azaspirodecane
  • Dialkylarylamine
  • Piperidinedione
  • N-alkylpiperazine
  • Piperidinone
  • Dicarboximide
  • Delta-lactam
  • Pyrimidine
  • Piperidine
  • Carboxylic acid imide, n-substituted
  • Heteroaromatic compound
  • Carboxylic acid imide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Anti-anxiety Agents
  • Anxiolytics sedatives and hypnotics
  • Serotonin Agonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point201.5 - 202.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.88e-01 g/LNot Available
LogP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.59 mg/mLALOGPS
logP1.95ALOGPS
logP1.78ChemAxon
logS-2.8ALOGPS
pKa (Strongest Basic)7.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area69.64 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity108.89 m3·mol-1ChemAxon
Polarizability44.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-004i-6940000000-197b8ea9ac79cbda753bView in MoNA
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00490
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00490
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00490
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2383
KEGG Compound IDC06861
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBuspirone
NuGOwiki LinkHMDB14633
Metagene LinkHMDB14633
METLIN IDNot Available
PubChem Compound2477
PDB IDNot Available
ChEBI ID3223
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. 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. [15640381 ]
  2. 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. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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. [19934256 ]
  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. [15640381 ]
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
References
  1. 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. [15640381 ]
General function:
Involved in monooxygenase activity
Specific function:
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.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular weight:
50618.9
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. [12781354 ]
  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. [11421254 ]
  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. [11224194 ]
  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. [14522358 ]
  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. [16214127 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
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
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular weight:
46106.3
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. [10027850 ]
  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. [10064829 ]
  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. [10215901 ]
  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. [10221756 ]
  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. [10428422 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [14769835 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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. [12438524 ]