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
Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors.	1999 Jun	10350034
5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats.	2000 Dec	11220492
Synthesis and pharmacological evaluation of aryl/heteroaryl piperazinyl alkyl benzotriazoles as ligands for some serotonin and dopamine receptor subtypes.	2001 Apr	11421254
Switching from benzodiazepines to buspirone using a tapered overlap method in generalized anxiety disorder.	2001 Aug	11561943
An open study of buspirone augmentation of neuroleptics in patients with schizophrenia.	2001 Aug	11476132
Serotonergic regulation of inhibitory avoidance and one-way escape in the rat elevated T-maze.	2001 Dec	11801289
The impact of impulsivity on cocaine use and retention in treatment.	2001 Dec	11777668
Effect of nonnicotine pharmacotherapy on smoking behavior.	2001 Dec	11765304
Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults.	2001 Dec	11762563
Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice.	2001 Feb	11243491
Prenatal stress and postnatal development of neonatal rats--sex-dependent effects on emotional behavior and learning ability of neonatal rats.	2001 Feb	11226753
Treatment of the agitation of late-life psychosis and Alzheimer's disease.	2001 Jan	11520475
Use of negatively reinforcing electrical brain stimulation to detect conventional and nonconventional anxiolytics as well as an anxiogenic drug.	2001 Jan	11274705
Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?	2001 Jul	11549229
Late-onset bipolar disorder due to hyperthyroidism.	2001 Jul	11437754
Serotonin-based pharmacotherapy for acute neuroleptic-induced akathisia: a new approach to an old problem.	2001 Jul	11435260
Is imipramine or buspirone treatment effective in patients wishing to discontinue long-term benzodiazepine use?	2001 Mar	11252203
Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder.	2001 Nov	11775049
A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?	2001 Oct	11564001
Bupropion-induced acute dystonia.	2002 Feb	11847943
Benzodiazepine discontinuation in generalized anxiety disorder.	2002 Feb	11823290
Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist.	2002 Jan	11805862
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 Jan-Feb	11812524

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