Betahist Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism Action: Betahistine dihydrochloride is an analog of histamine which can be administered orally. It was developed as one of several β-2-pyridyl alkylamine compounds with actions qualitatively similar to histamine but easier to administer than histamine itself; histamine is ineffective by the oral route. Betahistine is structurally similar to histamine.
The primary clinical indication for betahistine has been Meniere’s disease. Animal studies have demonstrated that betahistine induces histamine-like effects on inner ear microcirculation. Vasodilation of capillaries/arterioles of the spiral ligament and stria vascularis was reported with topical or IV use in guinea pigs and electrical impedance plethysmograph studies suggested increases in cochlear blood flow by over 200% in the same animal model following IV betahistine.
Betahistine has also been evaluated in cerebrovascular disease. Cerebral vasodilation has been reported in animals and humans following oral or IV betahistine, including patients with arteriosclerotic dementia. Oral administration of betahistine 32 mg daily for 1 week was reported to significantly increase cerebral blood flow in patients with ischemic cerebrovascular disease; however, focal decreases in blood flow have also been observed, suggesting intracerebral “steal” may also be operative.
Betahistine appears to act predominantly as a histamine-1 (H₁) receptor agonist. However, agonist activity at H₂ and H₃ receptors has also been reported. In 1 study, cimetidine reversed betahistine-induced relaxation of the rat uterus contracted by acetylcholine; chronotropic effects of betahistine on guinea pig atria were blocked by the H₂-receptor antagonist YM11170.
Similar to histamine, reduced blood pressure, headache and flushing occur after IV betahistine administration. However, it is claimed overall to be less toxic than histamine itself. With oral betahistine, gastrointestinal intolerance is the most frequent adverse effect; blood pressure is not generally affected to a significant degree. In contrast to histamine, betahistine has not been reported to significantly increase gastric acid secretion in small studies.
Pharmacokinetics: Pharmacokinetic data for betahistine are limited; Betahist Forte is rapidly absorbed after oral doses and converted to at least 2 metabolites. It is unclear if metabolites are pharmacologically active. Most of a dose is excreted via the urine as metabolites. An elimination half-life (t_½) of 3.5 hrs has been reported.