DrugBank: Betahistine (DB06698)

targets (2)

Identification

Name

Betahistine

Accession Number

DB06698

Type

small molecule

Groups

approved

Description

Betahistine is an antivertigo drug first used for treating vertigo assosicated with Ménière’s disease. It is also commonly used for patients with balance disorders.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Salts

Not Available

Brand names

Name	Company
Serc	Abbott Products

Brand mixtures

Not Available

Categories

Antivertigo Agents

CAS number

5638-76-6

Weight

Average: 136.1943
Monoisotopic: 136.100048394

Chemical Formula

C₈H₁₂N₂

InChI Key

InChIKey=UUQMNUMQCIQDMZ-UHFFFAOYSA-N

InChI

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

Plain Text

IUPAC Name

methyl[2-(pyridin-2-yl)ethyl]amine

SMILES

CNCCC1=CC=CC=N1

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Pyridines and Derivatives

Substructures

Aliphatic and Aryl Amines
Pyridines and Derivatives
Heterocyclic compounds
Aromatic compounds
Imines

Pharmacology

Indication

For the reduction of episodes of vertigo association with Ménière's disease.

Pharmacodynamics

Betahistine primarily acts as a histamine H1-agonist with 0.07 times the activity of histamine. Stimulating the H1-receptors in the inner ear causes a vasodilatory effect and increased permeability in the blood vessels which results in reduced endolymphatic pressure. Betahistine is believed to act by reducing the asymmetrical functioning of sensory vestibular organs as well as by increasing vestibulocochlear blood flow. Doing so aids in decreasing symptoms of vertigo and balance disorders. Betahistine also acts as a histamine H3-receptor antagonist which causes an increased output of histamine from histaminergic nerve endings which can further increase the direct H1-agonist activity. Furthermore, H3-receptor antagonism increases the levels of neurotransmitters such as serotonin in the brainstem, which inhibits the activity of vestibular nuclei, helping to restore proper balance and decrease in vertigo symptoms.

Mechanism of action

Not Available

Absorption

When given orally, betahistine is rapidly absorbed from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

Very low.

Metabolism

Betahistine is metabolized primarily into 2-pyridylacetic acid and is subsequently excreted in the urine.

Route of elimination

Renal

Half life

3-4 hours

Clearance

Not Available

Toxicity

Symptoms of overdose (< 640 mg) include mild to moderate nausea, dry mouth, dyspepsia, abdominal pain and somnolence. More serious complications such as convulsions, pulmonary or cardiac complications, may occur with higher intentional overdoses (> 640 mg).

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Abbott products inc
Teva Pharmaceuticals

Packagers

Not Available

Dosage forms

Form	Route	Strength
Tablet	Oral	8mg, 16mg, 24mg

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
logP	0.68	YOUNG,RC ET AL. (1993)
pKa	10.1 (at 10 °C)	PERRIN,DD (1965)

Predicted Properties

Property	Value	Source
water solubility	4.93e+01 g/l	ALOGPS
logP	0.59	ALOGPS
logP	0.63	ChemAxon
logS	-0.44	ALOGPS
pKa (strongest basic)	9.77	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	2	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	24.92	ChemAxon
rotatable bond count	3	ChemAxon
refractivity	41.33	ChemAxon
polarizability	15.85	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Health Canada

External Links

Resource	Link
KEGG Drug	D07522
PubChem Compound	2366
PubChem Substance	99443252
ChemSpider	2276
ChEBI	35677
ChEMBL	35677
PharmGKB	PA165958372
Wikipedia	http://en.wikipedia.org/wiki/Betahistine

ATC Codes

N07CA01

AHFS Codes

92:00.00

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Take with food.

Targets
1. Histamine H1 receptor Pharmacological action: yes Actions: agonist In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system Organism class: human UniProt ID: P35367 Gene: HRH1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Serc monograph. (2010). [Electronic version]. e-CPS. Retrieved November 28, 2010. Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed Lacour M, Sterkers O: Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action. CNS Drugs. 2001;15(11):853-70. Pubmed 2. Histamine H3 receptor Pharmacological action: yes Actions: antagonist The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 niether modified adenylate cyclase activity nor induced intracellular calcium mobilization Organism class: human UniProt ID: Q9Y5N1 Gene: HRH3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed Lacour M, Sterkers O: Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action. CNS Drugs. 2001;15(11):853-70. Pubmed Gbahou F, Davenas E, Morisset S, Arrang JM: Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo. J Pharmacol Exp Ther. 2010 Sep 1;334(3):945-54. Epub 2010 Jun 8. Pubmed

Targets

1. Histamine H1 receptor

Pharmacological action: yes
Actions: agonist

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out

Gene: HRH1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Serc monograph. (2010). [Electronic version]. e-CPS. Retrieved November 28, 2010.
Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed
Lacour M, Sterkers O: Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action. CNS Drugs. 2001;15(11):853-70. Pubmed

2. Histamine H3 receptor

Pharmacological action: yes
Actions: antagonist

The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 niether modified adenylate cyclase activity nor induced intracellular calcium mobilization

Organism class: human
UniProt ID: Q9Y5N1 Link_out

Gene: HRH3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed
Lacour M, Sterkers O: Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action. CNS Drugs. 2001;15(11):853-70. Pubmed
Gbahou F, Davenas E, Morisset S, Arrang JM: Effects of betahistine at histamine H3 receptors: mixed inverse agonism/agonism in vitro and partial inverse agonism in vivo. J Pharmacol Exp Ther. 2010 Sep 1;334(3):945-54. Epub 2010 Jun 8. Pubmed

Comments

Drug created on May 06, 2010 10:01 / Updated on February 08, 2013 16:24