BETAHISTINE MALEATE

First approved in 1966

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H12N2.C4H4O4
Molecular Weight	252.2664
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CNCCC1=CC=CC=N1

InChI

InChIKey=JLPICNMNXPSXMA-BTJKTKAUSA-N

InChI=1S/C8H12N2.C4H4O4/c1-9-7-5-8-4-2-3-6-10-8;5-3(6)1-2-4(7)8/h2-4,6,9H,5,7H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C8H12N2
Molecular Weight	136.1943
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2990946
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11700150 | https://www.ncbi.nlm.nih.gov/pubmed/18447604 | https://www.ncbi.nlm.nih.gov/pubmed/19300572

Betahistine is an orally administered, centrally acting histamine H1 receptor agonist with partial H3 antagonistic activity. It is proposed that betahistine may reduce peripherally the asymmetric functioning of the sensory vestibular organs in addition to increasing vestibulocochlear blood flow by antagonising local H3 heteroreceptors. Betahistine acts centrally by enhancing histamine synthesis within tuberomammillary nuclei of the posterior hypothalamus and histamine release within vestibular nuclei through antagonism of H3 autoreceptors. This mechanism, together with less specific effects of betahistine on alertness regulation through cerebral H1 receptors, should promote and facilitate central vestibular compensation. Betahistine is used to treat the symptoms associated with Ménière's disease, a condition of the inner ear which causes, vertigo (dizziness), tinnitus (ringing in the ears), hearing loss.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H3 receptor 44 Target ID: CHEMBL5076 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18447604 \| https://www.ncbi.nlm.nih.gov/pubmed/2990946	Agonist 2678		31.0 µM [Ki]
Histamine H3 receptor 44 Target ID: CHEMBL4124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18447604 \| https://www.ncbi.nlm.nih.gov/pubmed/2990946	Antagonist 2778		6.9 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Meniere's disease 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19300572 https://www.ncbi.nlm.nih.gov/pubmed/11677834 https://www.ncbi.nlm.nih.gov/pubmed/17061910	Primary		Approved 8429	Betahistine Approved Use Betahistine is used to treat the symptoms associated with Ménière's disease, a condition of the inner ear which causes, vertigo (dizziness), tinnitus (ringing in the ears), hearing loss. Launch Date 1968

C_max

Value	Dose	Co-administered	Analyte	Population
339.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14765546/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		2-PYRIDINEACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1196 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14765546/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		2-PYRIDINEACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14765546/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		2-PYRIDINEACETIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
72 mg 3 times / day multiple, oral Highest studied dose Dose: 72 mg, 3 times / day Route: oral Route: multiple Dose: 72 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1958439/	healthy, 20-31 n = 12 Health Status: healthy Age Group: 20-31 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1958439/	Sources: https://pubmed.ncbi.nlm.nih.gov/1958439/
728 mg 1 times / day single, oral Overdose Dose: 728 mg, 1 times / day Route: oral Route: single Dose: 728 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17061910/	healthy, adult n = 1 Health Status: healthy Age Group: adult Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17061910/	Sources: https://pubmed.ncbi.nlm.nih.gov/17061910/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 147	inhibitor 3277 Sources: https://www.medicines.org.uk/emc/product/4038/smpc, http://www.auropharma.ca/products/monograph/Auro-Betahistine-PM.pdf	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:35677	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:35677
ChemicalBook	CB4489793	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4489793
MolPort	MolPort-000-142-007	https://www.molport.com/shop/molecule-link/MolPort-000-142-007
ZINC	ZINC000001675415	http://zinc15.docking.org/substances/ZINC000001675415
eMolecules	591762	https://www.emolecules.com/cgi-bin/more?vid=591762

PubMed

Title	Date	PubMed
[Acute dystonia secondary to treatment with betahistine].	2000 Nov	11195153
[Menière's disease. Current status].	2001	11799866
Betahistine produces post-synaptic inhibition of the excitability of the primary afferent neurons in the vestibular endorgans.	2001	11677735
[Betaserk efficiency in cochlear and vestibular disorders in the regional surdocenter].	2001	11510053
Effect of positively and negatively charged liposomes on skin permeation of drugs.	2001	11378523
Binding affinity profile of betahistine and its metabolites for central histamine receptors of rodents.	2001 Apr	11352543
Pressure treatment versus gentamicin for Meniere's disease.	2001 Jan	11349793
The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training.	2001 Jul	11583395
Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches.	2001 Jun	11677834
Initial structure-activity relationship studies of a novel series of pyrrolo[1,2-a]pyrimid-7-ones as GnRH receptor antagonists.	2002 Feb 11	11814806
Menière's disease in the elderly.	2002 Jan	11773851
Homeopathic vs conventional treatment of vertigo.	2003 Apr	12707212
Evaluation of a sol-gel derived carbon composite electrode as an amperometric detector for capillary electrophoresis.	2003 Mar 28	12703905
Betahistine in vertebrobasilar insufficiency.	2004	15732521
Investigation of Betaserc in auditory and vestibular disturbances.	2004	15732519
[A use of betaserc in ataxic syndromes].	2004	15554141
[The role of betaserk in combined treatment of neurosensory hypoacusis and vestibulopathy in childhood].	2004	15111941
Menière's disease.	2004 Jun	15652027
[Delirium in a 73-year-old man after many years of unwise use of betahistine].	2004 Nov 20	15587054
[Clinico-neurological and stabilometric analysis of betahistine (betaserc) efficacy in the patients with vertigo in the rehabilitation period of ischemic stroke].	2005	16447551
[Epidemiology, clinical features and betaserc therapy of vertigo in initial and reversible cerebrovascular pathology].	2005	16250576
Histamine (H3) receptors modulate the excitatory amino acid receptor response of the vestibular afferents.	2005 Dec 7	16310756
The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.	2005 Mar	15729086
Dose- and duration-dependent effects of betahistine dihydrochloride treatment on histamine turnover in the cat.	2005 Oct 31	16226741
[Clinical effectiveness of betahistine in monotherapy of vertigo for different etiology].	2006	17357686
[Betaserk in therapy of cochleovestibular disordes].	2006	17152479
Betahistine: a retrospective synopsis of safety data.	2006	17061910
[Betaserc in the treatment of vestibular dysfunctions of different etiology].	2006	16482015
[Fluctuating deafness].	2006 Dec	17202986
Pharmacological advances in the treatment of neuro-otological and eye movement disorders.	2006 Feb	16415675
Role of H1 receptors in histamine-mediated up-regulation of STAT4 phosphorylation.	2006 Mar	16428084
Role of apolipoprotein E in anxiety.	2007	17710250
'Complementary ENT': a systematic review of commonly used supplements.	2007 Aug	17125579
Reversible sensorineural hearing loss in a girl with Kawasaki disease.	2007 Oct-Dec	18246748
A fixed combination of cinnarizine/dimenhydrinate for the treatment of patients with acute vertigo due to vestibular disorders : a randomized, reference-controlled clinical study.	2008	18211117
Case report: a case of intractable Meniere's disease treated with autogenic training.	2008 Jan 25	18221543

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose is one tablet (16mg) or two tablets (8mg) three times a day, preferably taken with meals.

Route of Administration: Oral

In Vitro Use Guide

Treatment with dimaprit at 6 and 60 uM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 uM under the same conditions did not affect it.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:56:49 GMT 2023` Edited by `admin` on `Sat Dec 16 17:56:49 GMT 2023`
Record UNII	U5SU5350VT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BETAHISTINE MALEATE

Common Name

English

2-PYRIDINEETHANAMINE, N-METHYL-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

SUZUTOLON [MI]

Brand Name

English

2-PYRIDINEETHANAMINE, N-METHYL-, (Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

Betahistine maleate [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

54588573