Betahistine

Names

[ Name ]:
Betahistine

[Synonym ]:
2-(b-Methylaminoethyl)pyridine
N-methyl-2-pyridin-2-ylethanamine
Pyridine, 2-[2- (methylamino)ethyl]-
MFCD00006362
N-Methyl-2-(2-pyridinyl)ethanamine
EINECS 227-086-4
Suzutolon
2-Pyridineethanamine, N-methyl-
2-(2-Methylaminoethyl)pyridine
N-methyl-2-(pyridin-2-yl)ethanamine
N-Methyl-2-pyridineethanamine
Betahistine

Biological Activity

[Description]:

Betahistine is an orally active histamine H1 receptor agonist and a H3 receptor antagonist[1]. Betahistine is used for the study of rheumatoid arthritis (RA)[3].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

[Target]

H1 Receptor

H3 receptor

[In Vitro]

Betahistine (0-10 μM) inhibits [125I]iodoproxyfan binding to membranes of CHO (rH3(445)R) and CHO (hH3(445)R) cells with IC50 values of 1.9 μM and 3.3 μM, respectively. Lead to Ki values of 1.4 μM and 2.5 μM, respectively[2]. Betahistine (0-10 μM) has a regulating function on cAMP formation in CHO (rH3(445)R), CHO (rH3(413)R), and CHO (hH3(445)R) cells. At low concentrations, betahistine behaves an apparent inverse agonist, and progressively enhances cAMP formation with EC50 values of 0.1 nM, 0.05 nM and 0.3 nM, respectively. In contrast, at concentrations higher than 10 nM, betahistine inhibits cAMP formation with an EC50 value of 0.1 μM in CHO (rH3(445)R) and full agonist activity[2].

[In Vivo]

Betahistine (intraperitoneal or oral administration; 0.1-30 mg/kg; single dose) with acute administration has increased tele-methylhistamine (t-MeHA) levels with an ED50 of 0.4 mg/kg, indicating the inverse agonism. Besides, after acute oral administration, it increases t-MeHA levels with an ED50 of 2 mg/kg in male Swissmice[2]. Betahistine (oral adminstration; 1 and 5 mg/kg; daily for 3 weeks) attenuates the severity of arthritis and reduces the levels of pro-inflammatory cytokines in the paw tissues of CIA mice[3]. Animal Model: Collagen-induced arthritis (CIA) DBA/1 male mouse model[3] Dosage: 1 mg/kg; 5mg/kg Administration: Oral adminstration; day 21 to day 42 after a 21-day CIA induction Result: Ameliorated mouse CIA by decreasing joint destruction.

[References]

[1]. Poyurovsky M, et al. The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients. Int Clin Psychopharmacol. 2005 Mar;20(2):101-3.

[2]. Gbahou F, et al. 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.

[3]. Tang KT, et al. Betahistine attenuates murine collagen-induced arthritis by suppressing both inflammatory and Th17 cell responses.Int Immunopharmacol. 2016 Oct;39:236-245.

Chemical & Physical Properties

[ Density]:
1.0±0.1 g/cm3

[ Boiling Point ]:
210.9±15.0 °C at 760 mmHg

[ Molecular Formula ]:
C₈H₁₂N₂

[ Molecular Weight ]:
136.194

[ Flash Point ]:
96.7±0.0 °C

[ Exact Mass ]:
136.100052

[ PSA ]:
24.92000

[ LogP ]:
0.10

[ Vapour Pressure ]:
0.2±0.4 mmHg at 25°C

[ Index of Refraction ]:
1.510

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UT5552000

CHEMICAL NAME :: Pyridine, 2-(2-(methylamino)ethyl)-

CAS REGISTRY NUMBER :: 5638-76-6

BEILSTEIN REFERENCE NO. :: 0112294

LAST UPDATED :: 199701

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C8-H12-N2

MOLECULAR WEIGHT :: 136.22

WISWESSER LINE NOTATION :: T6NJ B2M1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 6110 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PBFMAV Problemi na Farmatsiyata. Problems in Pharmacy. (Durzhavno Izdatel'stvo Meditsina i Fizkultura, Pl. Slaveikov II, Sofia, Bulgaria) V.1- 1973- Volume(issue)/page/year: 13,63,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 980 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PBFMAV Problemi na Farmatsiyata. Problems in Pharmacy. (Durzhavno Izdatel'stvo Meditsina i Fizkultura, Pl. Slaveikov II, Sofia, Bulgaria) V.1- 1973- Volume(issue)/page/year: 13,63,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2920 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PBFMAV Problemi na Farmatsiyata. Problems in Pharmacy. (Durzhavno Izdatel'stvo Meditsina i Fizkultura, Pl. Slaveikov II, Sofia, Bulgaria) V.1- 1973- Volume(issue)/page/year: 13,63,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 320 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PBFMAV Problemi na Farmatsiyata. Problems in Pharmacy. (Durzhavno Izdatel'stvo Meditsina i Fizkultura, Pl. Slaveikov II, Sofia, Bulgaria) V.1- 1973- Volume(issue)/page/year: 13,63,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 94500 mg/kg/90D-C

TOXIC EFFECTS :: Behavioral - muscle weakness Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 2,344,1968

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
Eyeshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
Xi: Irritant;C: Corrosive;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S37/39

[ RIDADR ]:
UN2735

[ WGK Germany ]:
2

[ RTECS ]:
UT5552000

[ HS Code ]:
2933399090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants.

Pharm. Dev. Technol. 17(5) , 583-93, (2012)

Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, bees...

Comparison of the therapeutic efficacy of a fixed low-dose combination of cinnarizine and dimenhydrinate with betahistine in vestibular neuritis: a randomized, double-blind, non-inferiority study.

Clin. Drug Investig. 32(6) , 387-99, (2012)

Vestibular neuritis (VN) is a strongly disabling disease of the peripheral vestibular system. Rapid and effective relief of symptoms is important to allow patients to promptly return to normal physica...

Betahistine or Cinnarizine for treatment of Meniere's disease.

Med. Arh. 66(6) , 396-8, (2012)

Meniere's disease is a condition with sudden attacks of vertigo with nausea and vomiting accompanied by loss of hearing and buzzing sensation in the ears, most commonly unilateral. The exact cause of ...