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

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
Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action.	2001	11700150
Betahistine for Menière's disease or syndrome.	2001	11279734
Pressure treatment versus gentamicin for Meniere's disease.	2001 Jan	11349793
Action mechanism of betahistine in the vestibular end organs.	2001 Jun	11677837
Effects of betahistine and of its metabolites on vestibular sensory organs.	2001 Jun	11677836
Betahistine in the treatment of vertigo. History and clinical implications of recent pharmacological researches.	2001 Jun	11677834
Fixed combination of cinnarizine and dimenhydrinate versus betahistine dimesylate in the treatment of Ménière's disease: a randomized, double-blind, parallel group clinical study.	2002	14763223
[Betaserc treatment of acute disorders of cerebral circulation with vestibulo-ataxic and cochleo-vestibular syndromes].	2002	12400131
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
Betahistine dihydrochloride interaction with the histaminergic system in the cat: neurochemical and molecular mechanisms.	2002 Jun 20	12098586
Histamine receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.	2002 Oct-Dec	12866807
[Comparative efficacy of betaserc and cinnarizine of vertigo in patients with migraine].	2003	12789824
Menière's disease.	2003 Jun	12967379
Double-blind, randomized, multicenter study comparing the effect of betahistine and flunarizine on the dizziness handicap in patients with recurrent vestibular vertigo.	2003 Jun	12875580
Evaluation of a sol-gel derived carbon composite electrode as an amperometric detector for capillary electrophoresis.	2003 Mar 28	12703905
[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
Acute and clinically relevant drug-induced liver injury: a population based case-control study.	2004 Jul	15206996
Usefulness of high doses of glucocorticoids and hyperbaric oxygen therapy in sudden sensorineural hearing loss treatment.	2004 Nov	15547420
[Delirium in a 73-year-old man after many years of unwise use of betahistine].	2004 Nov 20	15587054
[Epidemiology, clinical features and betaserc therapy of vertigo in initial and reversible cerebrovascular pathology].	2005	16250576
Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials.	2005	15727161
Benign paroxysmal positional vertigo: a study of two manoeuvres with and without betahistine.	2005 Apr	16116833
The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.	2005 Mar	15729086
[Assessment of betahistine dihydrochloride effectiveness in the treatment of disturbance of balance system, based on analysis of doctors and patients questionnaires results].	2006	17469244
Betahistine in the treatment of vertiginous syndromes: a meta-analysis.	2006 Aug	18236637
Pharmacological advances in the treatment of neuro-otological and eye movement disorders.	2006 Feb	16415675
[Assessment of betahistine dihydrochloride effectiveness in the treatment of vertigo of a different aetiology based on videonystagmography test results].	2006 Mar	16780265
[Current methods for diagnosis and treatment of iatrogenic ototoxicity].	2007	18175413
Patient baseline characteristics in an open-label multinational study of betahistine in recurrent peripheral vestibular vertigo: the OSVaLD study.	2007 Nov	17910803
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
Management of Ménière's disease in general practice: adherence to the UK National Health Service 'Prodigy' guidelines.	2008 Aug	18039416
Treating common ear problems in pregnancy: what is safe?	2008 Feb	18034353
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.

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