BUSPIRONE

First approved in 1986

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H31N5O2
Molecular Weight	385.5031
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1CC2(CCCC2)CC(=O)N1CCCCN3CCN(CC3)C4=NC=CC=N4

InChI

InChIKey=QWCRAEMEVRGPNT-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H31N5O2
Molecular Weight	385.5031
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018731s051lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1796057 https://www.ncbi.nlm.nih.gov/pubmed/6151170

Buspirone is the first of a new class of anxioselective agents, the azaspirodecanediones. Animal studies have suggested antianxiety activity and the absence of abuse potential. Behavioural, electrophysiological and receptor binding experiments gradually led to the idea that buspirone owes much of its anxiolytic activity to its ability to attenuate central 5-hydroxytryptamine neurotransmission. In vitro preclinical studies have shown that buspirone has a high affinity for serotonin (5-HT1A) receptors. Some studies do suggest that buspirone may have indirect effects on other neurotransmitter systems. 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. The drug was approved by FDA for the treatment of anxiety.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 177 Target ID: CHEMBL214 Sources: http://psychopharmacologyinstitute.com/cns-receptors/5-ht1a-receptors/	Partial Agonist 297		24.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 275 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c78cf4ff-51b2-851e-89cc-98ea543e3865	Primary		Approved 8583	BUSPIRONE HYDROCHLORIDE Approved Use Buspirone hydrochloride tablets are indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Launch Date 2001

C_max

Value	Dose	Co-administered	Analyte	Population
1.711 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11504277	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		BUSPIRONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.613 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11504277	15 mg 2 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BUSPIRONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
9.402 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11504277	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		BUSPIRONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.837 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11504277	15 mg 2 times / day steady-state, oral dose: 15 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		BUSPIRONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.062 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11504277	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		BUSPIRONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
14% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18731s39s45lbl.pdf			BUSPIRONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946		substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 446

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018731s051lbl.pdf#page=3 Page: 3.0	major	yes (co-administration study) Comment: coadministration of buspirone (10 mg as a single dose) with verapamil (80 mg t.i.d.) or diltiazem (60 mg t.i.d.) increased plasma buspirone concentrations; coadministration of buspirone (10 mg as a single dose) with erythromycin (1.5 g/day for 4 days) increased plasma buspirone concentrations (5-fold increase in Cmax and 6-fold increase in AUC); coadministration of buspirone (10 mg as a single dose) with itraconazole (200 mg/day for 4 days) increased plasma buspirone concentrations (13-fold increase in Cmax and 19-fold increase in AUC); coadministration of buspirone (2.5 or 5 mg b.i.d.) with nefazodone (250 mg b.i.d.) resulted in marked increases in plasma buspirone concentrations (increases up to 20-fold in Cmax and up to 50-fold in AUC); coadministration of buspirone (30 mg as a single dose) with rifampin (600 mg/day for 5 days) decreased the plasma concentrations (83.7% decrease in Cmax; 89.6% decrease in AUC); Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018731s051lbl.pdf#page=3 Page: 3.0
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15640381/	minor
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15640381/	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3223	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3223
ChemicalBook	CB1367137	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1367137
ChemicalBook	CB63118898	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB63118898
ChemicalBook	CB73118901	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB73118901
ChemicalBook	CB93118899	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB93118899
eMolecules	1933757	https://www.emolecules.com/cgi-bin/more?vid=1933757
ZINC	ZINC000001530571	http://zinc15.docking.org/substances/ZINC000001530571

PubMed

Title	Date	PubMed
Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury.	2002-04	11953006
Tandospirone potentiates the fluoxetine-induced increases in extracellular dopamine via 5-HT(1A) receptors in the rat medial frontal cortex.	2002-04	11792466
[New drugs for the treatment of functional dyspepsia].	2002-03-29	11917722
Estimation of buspirone-bovine serum albumin binding by affinity capillary electrophoresis.	2002-03-06	11876437
Contact leukoderma caused by buspirone patches.	2002-03	11911108
[The role of neuropeptide Y in anxiety].	2002-02-15	11842605
Olfactory-mediated fear-potentiated startle.	2002-02	11895182
Bupropion-induced acute dystonia.	2002-02	11847943
Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.	2002-02	11847528
Benzodiazepine discontinuation in generalized anxiety disorder.	2002-02	11823290
Anxiogenic activity of Myristica fragrans seeds.	2002-01-29	11812528
The stimulus effect of 5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline is similar to that of cocaine but different from that of amphetamine.	2002-01-29	11812524
Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608).	2002-01-25	11821022
Light-enhanced startle: further pharmacological and behavioral characterization.	2002-01	11862363
Atypical kinetics for a series of putative dopamine antagonists to reverse the low-magnitude Ca2+ phase in the dopamine-bound D2short receptor state.	2002-01	11862337
Effect of drug proportion and mixing time on the content uniformity of a low dose drug in a high shear mixer.	2002-01	11836931
Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist.	2002-01	11805862
Effects of cholecystokinin tetrapeptide (CCK(4)) and anxiolytic drugs on the electrically evoked [(3)H]5-hydroxytryptamine outflow from rat cortical slices.	2001-12-13	11730707
Serotonergic regulation of inhibitory avoidance and one-way escape in the rat elevated T-maze.	2001-12	11801289
The impact of impulsivity on cocaine use and retention in treatment.	2001-12	11777668
Effect of nonnicotine pharmacotherapy on smoking behavior.	2001-12	11765304
Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults.	2001-12	11762563
Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B.	2001-11-26	11718831
Effect of citalopram and buspirone on the antinociceptive action of analgesic drugs.	2001-11-06	11693737
Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder.	2001-11	11775049
Acoustic startle, conditioned startle potentiation and the effects of 8-OH-DPAT and buspirone in rats selectively bred for differences in 8-OH-DPAT-induced hypothermia.	2001-11	11742145
Quantifying the 5-HT1A agonist action of buspirone in man.	2001-11	11713611
Buspirone and meperidine synergistically reduce the shivering threshold.	2001-11	11682404
Venlafaxine and generalised anxiety disorder: new preparation. Minimise recourse to drugs.	2001-10	11824426
The effect of glucocorticoids on the anxiolytic efficacy of buspirone.	2001-10	11605098
A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?	2001-10	11564001
Small platform stress increases exploratory activity of mice in staircase test.	2001-10	11513357
Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.	2001-10	11500255
Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study.	2001-09	11681769
Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats.	2001-09	11566145
Behavioral and biochemical effects of L-tryptophan and buspirone in a model of cerebellar atrophy.	2001-08-18	11509189
Conformational analysis and pharmacophore design for selected 1-(2-pyrimidinyl)piperazine derivatives with sedative-hypnotic activity.	2001-08-15	11501794
Gepirone. Organon.	2001-08	11892924
Switching from benzodiazepines to buspirone using a tapered overlap method in generalized anxiety disorder.	2001-08	11561943
Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.	2001-08	11532381
A comparative multidose pharmacokinetic study of buspirone extended-release tablets with a reference immediate-release product.	2001-08	11504277
Ataxia from lithium toxicity successfully treated with high-dose buspirone: a single-case experimental design.	2001-08	11494197
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.	2001-07-20	11476759
Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?	2001-07	11549229
An open trial of divalproex sodium in autism spectrum disorders.	2001-07	11488363
An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice.	2001-06	11485052
Effect of anxiolytics on blood sugar level in rabbits.	2001-04	11491585
Treatment of the agitation of late-life psychosis and Alzheimer's disease.	2001-01	11520475
Controversies in dyspepsia.	2001	11718524
Overview of different pharmacotherapies for attaining remission in generalized anxiety disorder.	2001	11577786

Patents

Sample Use Guides

In Vivo Use Guide

The recommended initial dose is 15 mg daily (7.5 mg b.i.d.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day, as needed. The maximum daily dosage should not exceed 60 mg per day. In clinical trials allowing dose titration, divided doses of 20 mg to 30 mg per day were commonly employed.

Route of Administration: Oral

In Vitro Use Guide

Buspiron was incubated with hippocampal pyramidal cells at concentration of 50 uM. Buspirone was shown to attenuate the synaptic activation of cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:12:28 GMT 2025` Edited by `admin` on `Mon Mar 31 18:12:28 GMT 2025`
Record UNII	TK65WKS8HL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GEN-BUSPIRONE

Preferred Name

English

BUSPIRONE

Official Name

English

BUSPIRONE [VANDF]

Common Name

English

buspirone [INN]

Common Name

English

8-(4-(4-(2-PYRIMIDINYL)-1-PIPERIZINYL)BUTYL)-8-AZASPIRO(4,5)DECANE-7,9-DIONE

Systematic Name

English

BUSPIRONE [MI]

Common Name

English

BCI-024

Code

English

Buspirone [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QN05BE01