BUSPIRONE

First approved in 1986

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H31N5O2
Molecular Weight	385.5039
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CCC2(C1)CC(=O)N(CCCCN3CCN(CC3)c4ncccn4)C(=O)C2

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	385.5039
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:: 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 162 Target ID: CHEMBL214 Sources: http://psychopharmacologyinstitute.com/cns-receptors/5-ht1a-receptors/	Partial Agonist 259	Anxiety	24 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Anxiety 245 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c78cf4ff-51b2-851e-89cc-98ea543e3865	Primary	Serotonin 1a (5-HT1a) receptor	Approved 7997	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 985737600000

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 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 Health Status: unhealthy Age Group: 6–17 years Sex: M+F 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 Health Status: unhealthy 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 Health Status: unhealthy 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 Health Status: unhealthy 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 Health Status: unhealthy 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 1470		substrate 1038

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 346

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1470	substrate 2752 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018731s051lbl.pdf#page=3 Page: 3	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
CYP2D6 1038	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/15640381/	minor
CYP3A5 346	substrate 2752 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
ZINC	ZINC000001530571	http://zinc15.docking.org/substances/ZINC000001530571

PubMed

Title	Date	PubMed
Controversies in dyspepsia.	2001	11718524
Overview of different pharmacotherapies for attaining remission in generalized anxiety disorder.	2001	11577786
Separation anxiety disorder in children and adolescents: epidemiology, diagnosis and management.	2001	11460893
Effect of anxiolytics on blood sugar level in rabbits.	2001 Apr	11491585
Switching from benzodiazepines to buspirone using a tapered overlap method in generalized anxiety disorder.	2001 Aug	11561943
Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.	2001 Aug	11532381
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
Treatment of the agitation of late-life psychosis and Alzheimer's disease.	2001 Jan	11520475
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
Characterization of alpha1-adrenoceptor-mediated contraction in the mouse thoracic aorta.	2001 Jul 20	11476759
Effect of citalopram and buspirone on the antinociceptive action of analgesic drugs.	2001 Jul-Aug	11693737
Behavioral and biochemical effects of L-tryptophan and buspirone in a model of cerebellar atrophy.	2001 Jul-Aug	11509189
[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
Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study.	2001 Jun	11465522
Conformational analysis and pharmacophore design for selected 1-(2-pyrimidinyl)piperazine derivatives with sedative-hypnotic activity.	2001 Mar-Apr	11501794
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
Quantifying the 5-HT1A agonist action of buspirone in man.	2001 Nov	11713611
Buspirone and meperidine synergistically reduce the shivering threshold.	2001 Nov	11682404
Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B.	2001 Nov 26	11718831
Venlafaxine and generalised anxiety disorder: new preparation. Minimise recourse to drugs.	2001 Oct	11824426
The effect of glucocorticoids on the anxiolytic efficacy of buspirone.	2001 Oct	11605098
A double-blind placebo-controlled study of buspirone-stimulated prolactin release in non-ulcer dyspepsia--are central serotoninergic responses enhanced?	2001 Oct	11564001
Small platform stress increases exploratory activity of mice in staircase test.	2001 Oct	11513357
Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.	2001 Oct	11500255
Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study.	2001 Sep	11681769
Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats.	2001 Sep	11566145
[The role of neuropeptide Y in anxiety].	2001 Sep-Oct	11842605
Hypomania induced by herbal and pharmaceutical psychotropic medicines following mild traumatic brain injury.	2002 Apr	11953006
Tandospirone potentiates the fluoxetine-induced increases in extracellular dopamine via 5-HT(1A) receptors in the rat medial frontal cortex.	2002 Apr	11792466
Olfactory-mediated fear-potentiated startle.	2002 Feb	11895182
Bupropion-induced acute dystonia.	2002 Feb	11847943
Benzodiazepine discontinuation in generalized anxiety disorder.	2002 Feb	11823290
Light-enhanced startle: further pharmacological and behavioral characterization.	2002 Jan	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 Jan	11862337
Effect of drug proportion and mixing time on the content uniformity of a low dose drug in a high shear mixer.	2002 Jan	11836931
Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist.	2002 Jan	11805862
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
Anxiogenic activity of Myristica fragrans seeds.	2002 Jan-Feb	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 Jan-Feb	11812524
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 `Sat Jun 26 04:35:17 UTC 2021` Edited by `admin` on `Sat Jun 26 04:35:17 UTC 2021`
Record UNII	TK65WKS8HL
Record Status	`Validated (UNII)`
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Name

Type

Language

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

GEN-BUSPIRONE

Brand Name

English

Classification Tree Code System Code

WHO-VATC

QN05BE01