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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
Synonyms
SynonymLanguageCode
[2-(2-Pyridyl)ethyl]methylamineNot AvailableNot Available
2-(beta-Methylaminoethyl)pyridineNot AvailableNot Available
2-[2-(Methylamino)ethyl]pyridineNot AvailableNot Available
BetahistinaNot AvailableNot Available
BetahistinumNot AvailableNot Available
N-Methyl-2-(2-pyridinyl)ethanamineNot AvailableNot Available
N-Methyl-2-pyridineethanamineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
SercAbbott Products
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number5638-76-6
WeightAverage: 136.1943
Monoisotopic: 136.100048394
Chemical FormulaC8H12N2
InChI KeyUUQMNUMQCIQDMZ-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassAmines
Sub ClassAralkylamines
Direct ParentAralkylamines
Alternative Parents
Substituents
  • Aralkylamine
  • Pyridine
  • Heteroaromatic compound
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
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
Not Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9949
Blood Brain Barrier+0.9485
Caco-2 permeable+0.7747
P-glycoprotein substrateSubstrate0.5736
P-glycoprotein inhibitor INon-inhibitor0.9568
P-glycoprotein inhibitor IINon-inhibitor0.9843
Renal organic cation transporterInhibitor0.5858
CYP450 2C9 substrateNon-substrate0.7936
CYP450 2D6 substrateSubstrate0.7703
CYP450 3A4 substrateNon-substrate0.71
CYP450 1A2 substrateNon-inhibitor0.6919
CYP450 2C9 substrateNon-inhibitor0.9339
CYP450 2D6 substrateNon-inhibitor0.9345
CYP450 2C19 substrateNon-inhibitor0.9253
CYP450 3A4 substrateNon-inhibitor0.8961
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9759
Ames testNon AMES toxic0.8219
CarcinogenicityNon-carcinogens0.9557
BiodegradationNot ready biodegradable0.8351
Rat acute toxicity1.3795 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8518
hERG inhibition (predictor II)Non-inhibitor0.8184
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
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 Solubility49.3 mg/mLALOGPS
logP0.59ALOGPS
logP0.63ChemAxon
logS-0.44ALOGPS
pKa (Strongest Basic)9.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area24.92 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity41.33 m3·mol-1ChemAxon
Polarizability15.85 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesN07CA01
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
ArformoterolMay diminish the therapeutic effect of Beta2-Agonists.
AzelastineAntihistamines may diminish the therapeutic effect of Betahistine.
BrompheniramineAntihistamines may diminish the therapeutic effect of Betahistine.
CarbinoxamineAntihistamines may diminish the therapeutic effect of Betahistine.
CetirizineAntihistamines may diminish the therapeutic effect of Betahistine.
ChlorphenamineAntihistamines may diminish the therapeutic effect of Betahistine.
ClemastineAntihistamines may diminish the therapeutic effect of Betahistine.
CyclizineAntihistamines may diminish the therapeutic effect of Betahistine.
CyproheptadineAntihistamines may diminish the therapeutic effect of Betahistine.
DesloratadineAntihistamines may diminish the therapeutic effect of Betahistine.
DexbrompheniramineAntihistamines may diminish the therapeutic effect of Betahistine.
DimenhydrinateAntihistamines may diminish the therapeutic effect of Betahistine.
DoxylamineAntihistamines may diminish the therapeutic effect of Betahistine.
FenoterolMay diminish the therapeutic effect of Beta2-Agonists.
FexofenadineAntihistamines may diminish the therapeutic effect of Betahistine.
Fluticasone furoateMay diminish the therapeutic effect of Beta2-Agonists.
Fluticasone PropionateAntihistamines may diminish the therapeutic effect of Betahistine.
FormoterolMay diminish the therapeutic effect of Beta2-Agonists.
HydroxyzineAntihistamines may diminish the therapeutic effect of Betahistine.
IndacaterolMay diminish the therapeutic effect of Beta2-Agonists.
Ipratropium bromideMay diminish the therapeutic effect of Beta2-Agonists.
IsocarboxazidMAO Inhibitors may increase the serum concentration of Betahistine.
KetotifenAntihistamines may diminish the therapeutic effect of Betahistine.
LevocetirizineAntihistamines may diminish the therapeutic effect of Betahistine.
LinezolidMAO Inhibitors may increase the serum concentration of Betahistine.
LoratadineAntihistamines may diminish the therapeutic effect of Betahistine.
MeclizineAntihistamines may diminish the therapeutic effect of Betahistine.
MoclobemideMAO Inhibitors may increase the serum concentration of Betahistine.
OlopatadineAntihistamines may diminish the therapeutic effect of Betahistine.
OrciprenalineMay diminish the therapeutic effect of Beta2-Agonists.
PhenelzineMAO Inhibitors may increase the serum concentration of Betahistine.
PirbuterolMay diminish the therapeutic effect of Beta2-Agonists.
PizotifenAntihistamines may diminish the therapeutic effect of Betahistine.
ProcarbazineMAO Inhibitors may increase the serum concentration of Betahistine.
RasagilineMAO Inhibitors may increase the serum concentration of Betahistine.
SalbutamolMay diminish the therapeutic effect of Beta2-Agonists.
SalmeterolMay diminish the therapeutic effect of Beta2-Agonists.
SelegilineMAO Inhibitors may increase the serum concentration of Betahistine.
Tedizolid PhosphateMAO Inhibitors may increase the serum concentration of Betahistine.
TerbutalineMay diminish the therapeutic effect of Beta2-Agonists.
TranylcypromineMAO Inhibitors may increase the serum concentration of Betahistine.
TriprolidineAntihistamines may diminish the therapeutic effect of Betahistine.
Food Interactions
  • Take with food.

Targets

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

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Drug created on May 06, 2010 10:01 / Updated on September 16, 2013 18:04