BUSPIRONE HYDROCHLORIDE

First approved in 1986

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H31N5O2.ClH
Molecular Weight	421.964
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=RICLFGYGYQXUFH-UHFFFAOYSA-N

InChI=1S/C21H31N5O2.ClH/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;1H

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

Molecular Formula	ClH
Molecular Weight	36.461
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 172 Target ID: CHEMBL214 Sources: http://psychopharmacologyinstitute.com/cns-receptors/5-ht1a-receptors/	Partial Agonist 290		24.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 267 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c78cf4ff-51b2-851e-89cc-98ea543e3865	Primary		Approved 8429	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
1.613 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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

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

Doses

Dose	Population	Adverse events
30 mg 1 times / day steady, oral (median) Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28846022/	unhealthy, 6–17 years n = 334 Health Status: unhealthy Condition: generalized anxiety disorder Age Group: 6–17 years Sex: M+F Population Size: 334 Sources: https://pubmed.ncbi.nlm.nih.gov/28846022/	Other AEs: Headache, Asthenia... Other AEs: Headache (29 patients) Asthenia (10 patients) Accidental injury (16 patients) Nausea (13 patients) Dyspepsia (5 patients) Diarrhea (6 patients) Vomiting (34 patients) Lightheadedness (14 patients) Somnolence (5 patients) Insomnia (5 patients) Nervousness (5 patients) Upper respiratory tract infection (5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/28846022/
15 mg 2 times / day steady, oral Dose: 15 mg, 2 times / day Route: oral Route: steady Dose: 15 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02458469	unhealthy n = 10 Health Status: unhealthy Condition: Spinal Cord Injury Population Size: 10 Sources: https://clinicaltrials.gov/ct2/show/NCT02458469	Other AEs: Nausea, Headache... Other AEs: Nausea (below serious, 1 patient) Headache (below serious, 1 patient) Fatigue (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02458469
20 mg 2 times / day steady, oral Dose: 20 mg, 2 times / day Route: oral Route: steady Dose: 20 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02132832	unhealthy n = 19 Health Status: unhealthy Condition: Marijuana Dependence Population Size: 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02132832	Other AEs: Light headedness... Other AEs: Light headedness (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02132832
30 mg 2 times / day steady, oral Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00875836	unhealthy n = 88 Health Status: unhealthy Condition: Marijuana Dependence Population Size: 88 Sources: https://clinicaltrials.gov/ct2/show/NCT00875836	Other AEs: Lightheadedness, Drowsiness... Other AEs: Lightheadedness (below serious, 36 patients) Drowsiness (below serious, 17 patients) Gastrointestinal disorder (below serious, 36 patients) Headache (below serious, 28 patients) Insomnia (below serious, 16 patients) Allergic sinusitis (below serious, 13 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00875836
30 mg 2 times / day steady, oral Dose: 30 mg, 2 times / day Route: oral Route: steady Dose: 30 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02803749	unhealthy n = 17 Health Status: unhealthy Condition: Parkinson's disease Population Size: 17 Sources: https://clinicaltrials.gov/ct2/show/NCT02803749	Other AEs: Frozen gait, Tremor... Other AEs: Frozen gait (below serious, 5 patients) Tremor (below serious, 3 patients) Dizziness (below serious, 2 patients) Fatigue (below serious, 2 patients) Bradycardia (below serious, 1 patient) Constipation (below serious, 1 patient) Dysphagia (below serious, 1 patient) Gastritis and duodenitis (below serious, 1 patient) Gastrointestinal disorder (NOS) (below serious, 1 patient) Cramp in hand (below serious, 1 patient) Headache (below serious, 1 patient) Increased agitation (below serious, 1 patient) Increased appetite (below serious, 1 patient) Balance impaired NOS (below serious, 1 patient) Dystonia (below serious, 1 patient) Irritability (below serious, 1 patient) Pain in knee (below serious, 1 patient) Pain (below serious, 1 patient) Insomnia (below serious, 1 patient) Joint stiffness (below serious, 1 patient) Pain neck/shoulder (below serious, 1 patient) Leg pain (below serious, 1 patient) Nasal congestion (below serious, 1 patient) Numbness (below serious, 1 patient) Infection respiratory (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02803749

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737		substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 395

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 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 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15640381/	minor
CYP3A5 395	substrate 3367 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
ZINC	ZINC000001530571	http://zinc15.docking.org/substances/ZINC000001530571
eMolecules	1933757	https://www.emolecules.com/cgi-bin/more?vid=1933757

PubMed

Title	Date	PubMed
5-HT1A receptor agonists buspirone and gepirone attenuate apomorphine-induced aggressive behaviour in adult male Wistar rats.	2000 Dec	11220492
Reversal of morphine-induced apnea in the anesthetized rat by drugs that activate 5-hydroxytryptamine(1A) receptors.	2000 Feb	10640309
Effects of serotoninergic drugs on tremor induced by physostigmine in rats.	2000 May	10762688
Separation anxiety disorder in children and adolescents: epidemiology, diagnosis and management.	2001	11460893
Pharmacotherapy of generalized anxiety disorder.	2001	11414551
Strategies for the treatment of antidepressant-related sexual dysfunction.	2001	11229451
Effect of anxiolytics on blood sugar level in rabbits.	2001 Apr	11491585
Molecular dynamics of buspirone analogues interacting with the 5-HT1A and 5-HT2A serotonin receptors.	2001 Apr	11354671
Gepirone. Organon.	2001 Aug	11892924
A comparative multidose pharmacokinetic study of buspirone extended-release tablets with a reference immediate-release product.	2001 Aug	11504277
Ataxia from lithium toxicity successfully treated with high-dose buspirone: a single-case experimental design.	2001 Aug	11494197
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
Effects of cholecystokinin tetrapeptide (CCK(4)) and anxiolytic drugs on the electrically evoked [(3)H]5-hydroxytryptamine outflow from rat cortical slices.	2001 Dec 13	11730707
Prenatal stress and postnatal development of neonatal rats--sex-dependent effects on emotional behavior and learning ability of neonatal rats.	2001 Feb	11226753
Female sexual dysfunction and antidepressant use.	2001 Feb	11156829
Recovery from chronic fatigue syndrome associated with changes in neuroendocrine function.	2001 Jan	11220065
An open trial of divalproex sodium in autism spectrum disorders.	2001 Jul	11488363
Pharmacokinetics of buspirone extended-release tablets: a single-dose study.	2001 Jul	11452712
Common effects of chronically administered antipanic drugs on brainstem GABA(A) receptor subunit gene expression.	2001 Jul	11443524
Late-onset bipolar disorder due to hyperthyroidism.	2001 Jul	11437754
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.	2001 Jul 20	11476759
[New drugs for the treatment of functional dyspepsia].	2001 Jul-Sep	11917722
An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice.	2001 Jun	11485052
SSRI discontinuation and buspirone.	2001 Jun	11384915
Potential involvement of S100B in the protective effects of a serotonin-1a agonist on ethanol-treated astrocytes.	2001 Jun 29	11412901
S 14506: novel receptor coupling at 5-HT(1A) receptors.	2001 Mar	11166326
Conformational analysis and pharmacophore design for selected 1-(2-pyrimidinyl)piperazine derivatives with sedative-hypnotic activity.	2001 Mar-Apr	11501794
Quantifying drug-related 5-HT1A receptor occupancy with.	2001 May	11401009
5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential.	2001 May 25	11408031
Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder.	2001 Nov	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 Nov	11742145
Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B.	2001 Nov 26	11718831
Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.	2001 Oct	11500255
Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats.	2001 Sep	11566145
Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury.	2002 Apr	11953006
Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608).	2002 Jan 25	11821022
Contact leukoderma caused by buspirone patches.	2002 Mar	11911108

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 `Fri Dec 15 15:48:12 GMT 2023` Edited by `admin` on `Fri Dec 15 15:48:12 GMT 2023`
Record UNII	207LT9J9OC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BUSPIRONE HYDROCHLORIDE

Official Name

English

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

Common Name

English

BUSPAR

Brand Name

English

BUSPIRONE HYDROCHLORIDE [MART.]

Common Name

English

MJ 9022-1

Code

English

BUSPIRONE HYDROCHLORIDE [VANDF]

Common Name

English

Buspirone hydrochloride [WHO-DD]

Common Name

English

BUSPIRONE HYDROCHLORIDE [USP-RS]

Common Name

English

BUSPIRONE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

BUSPIRONE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

N-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-1,1-cyclopentanediacetamide monohydrochloride

Systematic Name

English

APD-405

Code

English

BUSPIRONE HCL

Common Name

English

APD405

Code

English

BUSPIRONE HYDROCHLORIDE [USAN]

Common Name

English

NSC-759571

Code

English

BUSPIRONE HYDROCHLORIDE [MI]

Common Name

English

BUSPIRONE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

NSC-751138

Code

English

MJ-9022-1

Code

English

BUSPIRONE HYDROCHLORIDE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C28197