Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameBetahistine
Accession NumberDB06698
Typesmall molecule
Groupsapproved
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
Thumb
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
SercAbbott Products
Brand mixturesNot Available
CategoriesNot Available
CAS number5638-76-6
WeightAverage: 136.1943
Monoisotopic: 136.100048394
Chemical FormulaC8H12N2
InChI KeyInChIKey=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
IUPAC Name
methyl[2-(pyridin-2-yl)ethyl]amine
SMILES
CNCCC1=CC=CC=N1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassNot Available
Direct parentPyridines and Derivatives
Alternative parentsPolyamines; Dialkylamines
Substituentspolyamine; secondary aliphatic amine; secondary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the pyridines and derivatives. These are compounds containing a pyridine ring, which is a six-member aromatic heterocycle which consists of one nitrogen atom and five carbon atoms.
Pharmacology
IndicationFor the reduction of episodes of vertigo association with Ménière's disease.
PharmacodynamicsBetahistine 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 actionNot Available
AbsorptionWhen given orally, betahistine is rapidly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingVery low.
Metabolism

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

SubstrateEnzymesProduct
Betahistine
    2-pyridylacetic acidDetails
    Route of eliminationRenal
    Half life3-4 hours
    ClearanceNot Available
    ToxicitySymptoms 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
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9949
    Blood Brain Barrier + 0.9485
    Caco-2 permeable + 0.7747
    P-glycoprotein substrate Substrate 0.5736
    P-glycoprotein inhibitor I Non-inhibitor 0.9568
    P-glycoprotein inhibitor II Non-inhibitor 0.9843
    Renal organic cation transporter Inhibitor 0.5858
    CYP450 2C9 substrate Non-substrate 0.7936
    CYP450 2D6 substrate Substrate 0.7703
    CYP450 3A4 substrate Non-substrate 0.71
    CYP450 1A2 substrate Non-inhibitor 0.6919
    CYP450 2C9 substrate Non-inhibitor 0.9339
    CYP450 2D6 substrate Non-inhibitor 0.9345
    CYP450 2C19 substrate Non-inhibitor 0.9253
    CYP450 3A4 substrate Non-inhibitor 0.8961
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9759
    Ames test Non AMES toxic 0.8219
    Carcinogenicity Non-carcinogens 0.9557
    Biodegradation Not ready biodegradable 0.8351
    Rat acute toxicity 1.3795 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.8518
    hERG inhibition (predictor II) Non-inhibitor 0.8184
    Pharmacoeconomics
    Manufacturers
    • Abbott products inc
    • Teva Pharmaceuticals
    PackagersNot Available
    Dosage forms
    FormRouteStrength
    TabletOral8mg, 16mg, 24mg
    PricesNot Available
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    logP0.68YOUNG,RC ET AL. (1993)
    pKa10.1 (at 10 °C)PERRIN,DD (1965)
    Predicted Properties
    PropertyValueSource
    water solubility4.93e+01 g/lALOGPS
    logP0.59ALOGPS
    logP0.63ChemAxon
    logS-0.44ALOGPS
    pKa (strongest basic)9.77ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count1ChemAxon
    polar surface area24.92ChemAxon
    rotatable bond count3ChemAxon
    refractivity41.33ChemAxon
    polarizability15.85ChemAxon
    number of rings1ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterNoChemAxon
    Veber's ruleYesChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Jean S. Cherqui, Alain C. Djiane, “New galenical form of administration of betahistine and its derivatives and the preparation thereof.” U.S. Patent US4264574, issued February, 1979.

    US4264574
    General Reference
    1. Health Canada
    External Links
    ResourceLink
    KEGG DrugD07522
    PubChem Compound2366
    PubChem Substance99443252
    ChemSpider2276
    ChEBI35677
    ChEMBLCHEMBL24441
    PharmGKBPA165958372
    WikipediaBetahistine
    ATC CodesN07CA01
    AHFS Codes
    • 92:00.00
    PDB EntriesNot Available
    FDA labelNot Available
    MSDSNot Available
    Interactions
    Drug InteractionsNot Available
    Food InteractionsNot Available

    1. Histamine H1 receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    Histamine H1 receptor P35367 Details

    References:

    1. Serc monograph. (2010). [Electronic version]. e-CPS. Retrieved November 28, 2010.
    2. Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed
    3. 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

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Histamine H3 receptor Q9Y5N1 Details

    References:

    1. Barak N: Betahistine: what’s new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. Pubmed
    2. 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
    3. 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 September 16, 2013 18:04