Background:

Betahistine dihydrochloride is a histamine H3 receptors inhibitor used as an antivertigo drug.Target: Histamine ReceptorBetahistine dihydrochloride, a structural analogue of histamine with weak histamine H(1) receptor agonist and more potent H(3) receptor antagonist properties. Betahistine dihydrochloride acts centrally by enhancing histamine synthesis within tuberomammillary nuclei of the posterior hypothalamus and histamine release within vestibular nuclei through antagonism of H(3) autoreceptors [1].Therapeutic effects of betahistine in vestibular disorders result from its antagonist properties at histamine H(3) receptors (H(3)Rs). On inhibition of cAMP formation and [(3)H]arachidonic acid release, betahistine behaved as a nanomolar inverse agonist and a micromolar agonist. After acute oral administration, Betahistine increased t-MeHA levels with an ED(50) of 2 mg/kg, a rightward shift probably caused by almost complete first-pass metabolism. Therapeutic effects of betahistine result from an enhancement of histamine neuron activity induced by inverse agonism at H(3) autoreceptors [2].

参考文献:
[1]. Lacour, M. and O. Sterkers, Histamine and betahistine in the treatment of vertigo: elucidation of mechanisms of action. CNS Drugs, 2001. 15(11): p. 853-70.
[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. 334(3): p. 945-54.