Identification

Name
Betahistine
Accession Number
DB06698
Type
Small Molecule
Groups
Approved, Investigational
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
  • [2-(2-Pyridyl)ethyl]methylamine
  • 2-(beta-Methylaminoethyl)pyridine
  • 2-[2-(Methylamino)ethyl]pyridine
  • Betahistina
  • Betahistinum
  • N-Methyl-2-(2-pyridinyl)ethanamine
  • N-Methyl-2-pyridineethanamine
Product Ingredients
IngredientUNIICASInChI Key
Betahistine hydrochloride49K58SMZ7U5579-84-0XVDFMHARQUBJRE-UHFFFAOYSA-N
Betahistine maleateU5SU5350VT133206-34-5JLPICNMNXPSXMA-BTJKTKAUSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act BetahistineTablet16 mgOralActavis Pharma Company2011-10-13Not applicableCanada
Act BetahistineTablet24 mgOralActavis Pharma Company2011-10-13Not applicableCanada
BetahistineTablet24 mgOralSanis Health Inc2018-03-07Not applicableCanada
BetahistineTablet16 mgOralSanis Health Inc2018-03-07Not applicableCanada
SercTablet16 mgOralBgp Pharma Ulc2001-08-17Not applicableCanada
SercTablet24 mgOralBgp Pharma Ulc2003-12-10Not applicableCanada
Serc - Tab 4mgTablet4 mgOralSolvay Pharma Inc1997-08-132001-03-22Canada
Serc 4mgTablet4 mgOralUnimed Pharmaceuticals1968-12-311996-09-10Canada
Serc 8 mgTablet8 mgOralSolvay Pharma Inc1999-09-272005-02-07Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-betahistineTablet8 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-betahistineTablet24 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-betahistineTablet16 mgOralApotex CorporationNot applicableNot applicableCanada
Auro-betahistineTablet8 mgOralAuro Pharma Inc2015-11-30Not applicableCanada
Auro-betahistineTablet24 mgOralAuro Pharma Inc2015-11-30Not applicableCanada
Auro-betahistineTablet16 mgOralAuro Pharma Inc2015-11-30Not applicableCanada
PMS-betahistineTablet24 mgOralPharmascience Inc2014-01-16Not applicableCanada
PMS-betahistineTablet16 mgOralPharmascience Inc2014-01-16Not applicableCanada
Teva-betahistineTablet24 mgOralTeva2006-08-30Not applicableCanada
Teva-betahistineTablet16 mgOralTeva2006-08-14Not applicableCanada
Categories
UNII
X32KK4201D
CAS number
5638-76-6
Weight
Average: 136.1943
Monoisotopic: 136.100048394
Chemical Formula
C8H12N2
InChI Key
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

Pharmacology

Indication

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

Associated Conditions
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
TargetActionsOrganism
AHistamine H1 receptor
agonist
Human
AHistamine H3 receptor
antagonist
Human
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
PathwayCategory
Betahistine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Betahistine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Betahistine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Betahistine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Betahistine.
AbediterolThe therapeutic efficacy of Abediterol can be decreased when used in combination with Betahistine.
AceprometazineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Aceprometazine.
AcrivastineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Acrivastine.
AlimemazineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Alimemazine.
AmitriptylineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Amitriptyline.
AmoxapineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Amoxapine.
Food Interactions
  • Take with food.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0015644
KEGG Drug
D07522
PubChem Compound
2366
PubChem Substance
99443252
ChemSpider
2276
BindingDB
96589
ChEBI
35677
ChEMBL
CHEMBL24441
PharmGKB
PA165958372
Wikipedia
Betahistine
ATC Codes
N07CA01 — Betahistine
AHFS Codes
  • 28:92.00 — Miscellaneous Central Nervous System Agents
  • 92:00.00 — Miscellaneous Therapeutic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
1CompletedTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Overnutrition1
2CompletedTreatmentAutism, Early Infantile / Bipolar I Disorder / Bipolar II / Bipolar NOS / Psychotic Disorder Not Otherwise Specified / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform / Schizophreniform Disorder1
2CompletedTreatmentBMI >30 kg/m22
2TerminatedPreventionWeight gain therapy1
2TerminatedTreatmentHigh Cholesterol1
Not AvailableRecruitingTreatmentDiseases affecting vestibular system1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral16 mg
TabletOral24 mg
TabletOral4 mg
TabletOral8 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9339
CYP450 2D6 inhibitorNon-inhibitor0.9345
CYP450 2C19 inhibitorNon-inhibitor0.9253
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
Pyridines and derivatives / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Aralkylamine / Pyridine / Heteroaromatic compound / Azacycle / Organoheterocyclic compound / Secondary amine / Secondary aliphatic amine / Organopnictogen compound / Hydrocarbon derivative / Aromatic heteromonocyclic compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
secondary amino compound, aminoalkylpyridine (CHEBI:35677)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Histamine receptor activity
Specific Function
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Barak N: Betahistine: what's new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. doi: 10.1517/13543784.17.5.795 . [PubMed:18447604]
  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:11700150]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
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 a...
Gene Name
HRH3
Uniprot ID
Q9Y5N1
Uniprot Name
Histamine H3 receptor
Molecular Weight
48670.81 Da
References
  1. Barak N: Betahistine: what's new on the agenda? Expert Opin Investig Drugs. 2008 May;17(5):795-804. doi: 10.1517/13543784.17.5.795 . [PubMed:18447604]
  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:11700150]
  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. doi: 10.1124/jpet.110.168633. Epub 2010 Jun 8. [PubMed:20530654]

Drug created on May 06, 2010 10:01 / Updated on November 12, 2018 07:32