BETAHISTINE

First approved in 1966

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H12N2
Molecular Weight	136.1943
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNCCC1=CC=CC=N1

InChI

InChIKey=UUQMNUMQCIQDMZ-UHFFFAOYSA-N

InChI=1S/C8H12N2/c1-9-7-5-8-4-2-3-6-10-8/h2-4,6,9H,5,7H2,1H3

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 -5.14944E10

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 receptor type coupled to nitric oxide-induced relaxation of guinea-pig nasal mucosa.	2002 Oct-Dec	12866807
Alternobaric oxygen therapy in long-term treatment of Ménière's disease.	2002 Winter	12797667
[Current approaches to the treatment of vertigo in children].	2003	14763257
Evaluation of betahistine for the prevention of seasickness: effect on vestibular function, psychomotor performance and efficacy at sea.	2003	14757913
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
[Cerebral hemodynamics and statokinetic functions in patients with vertebral basilar vascular insufficiency].	2004	15847325
Betahistine in vertebrobasilar insufficiency.	2004	15732521
Investigation of Betaserc in auditory and vestibular disturbances.	2004	15732519
Management of idiopathic sudden sensorineural hearing loss: experience in newly developing Qatar.	2004	15732516
[Betaserc treatment of psychogenic vertigo].	2004	15347033
[Rehabilitation of patients with peripheral vestibular disorders].	2004	15139364
Meniere's disease.	2004 Dec	15865674
Acute and clinically relevant drug-induced liver injury: a population based case-control study.	2004 Jul	15206996
Menière's disease.	2004 Jun	15652027
Usefulness of high doses of glucocorticoids and hyperbaric oxygen therapy in sudden sensorineural hearing loss treatment.	2004 Nov	15547420
Efficacy and Tolerability of a Fixed Combination of Cinnarizine and Dimenhydrinate versus Betahistine in the Treatment of Otogenic Vertigo : A Double-Blind, Randomised Clinical Study.	2005	17532678
[Clinico-neurological and stabilometric analysis of betahistine (betaserc) efficacy in the patients with vertigo in the rehabilitation period of ischemic stroke].	2005	16447551
[Efficacy of betaserk in experimental motor disease].	2005	16353011
[Betaserk in the treatment of aftereffects of craniocerebral injury and vascular events].	2005	16117150
[Betaserc and improvement of life quality in war veterans].	2005	15822746
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
Menière's disease.	2005 Dec	16620426
Histamine (H3) receptors modulate the excitatory amino acid receptor response of the vestibular afferents.	2005 Dec 7	16310756
A national survey amongst UK otolaryngologists regarding the treatment of Ménière's disease.	2005 Feb	15829061
Involvement of histamine H1 and H2 receptors in the regulation of STAT-1 phosphorylation: inverse agonism exhibited by the receptor antagonists.	2005 Jul	15914334
The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.	2005 Mar	15729086
Effects of betahistine on the spatiotemporal response properties of vestibulospinal neurons to labyrinthine volleys.	2005 May 16	15878499
[Vertigo attacks -- current therapy].	2005 Nov	16358192
Excitatory effect of histamine on neuronal activity of rat globus pallidus by activation of H2 receptors in vitro.	2005 Nov	16143415
West Nile virus infection and conjunctival exposure.	2005 Oct	16355512
[Assessment of betahistine dihydrochloride effectiveness in the treatment of disturbance of balance system, based on analysis of doctors and patients questionnaires results].	2006	17469244
[Clinical effectiveness of betahistine in monotherapy of vertigo for different etiology].	2006	17357686
[Betaserc in the treatment of vestibular dysfunctions of different etiology].	2006	16482015
[Efficacy of Betahistine Mesilate combined with Flunarizine Hydrochloride for treating tinnitus].	2006 Apr	16848175
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
Role of H1 receptors in histamine-mediated up-regulation of STAT4 phosphorylation.	2006 Mar	16428084
Restoration of vestibular function: basic aspects and practical advances for rehabilitation.	2006 Sep	16968568
Role of apolipoprotein E in anxiety.	2007	17710250
'Complementary ENT': a systematic review of commonly used supplements.	2007 Aug	17125579
Optimizing the pharmacological component of integrated balance therapy.	2007 Jan-Feb	17505593
Histaminergic ligands improve vestibular compensation in the cat: behavioural, neurochemical and molecular evidence.	2007 Jul 30	17573072
Histamine affects STAT6 phosphorylation via its effects on IL-4 secretion: role of H1 receptors in the regulation of IL-4 production.	2007 Mar	17276885
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
Improving the quality of life in patients with vestibular disorders: the role of medical treatments and physical rehabilitation.	2008 Jan	17537195
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

Official Name

English

N-METHYL-2-PYRIDINEETHANAMINE

Systematic Name

English

BETAHISTINE [MART.]

Common Name

English

BETAHISTINE [MI]

Common Name

English

NSC-42617

Code

English

2-(2-(METHYLAMINO)ETHYL)PYRIDINE

Systematic Name

English

HISTALEAN

Brand Name

English

Betahistine [WHO-DD]

Common Name

English

2-PYRIDINEETHANAMINE, N-METHYL-

Systematic Name

English

betahistine [INN]

Common Name

English

BETAHISTINE [VANDF]

Common Name

English

BETAHISTINE MESILATE [JAN]

Common Name

English

VESTIBO

Brand Name

English

Classification Tree Code System Code

WHO-VATC

QN07CA01