Verbeta-16/Verbeta-24 Mechanism of Action

Pharmacology: Mode of Action: The mode of action of Betahistine was believed to be a direct stimulating (agonistic) effect on H1 receptors located on blood vessels in the inner ear. This would give rise to local vasodilation and increased permeability, which would help reverse the underlying problem of endolymphatic hydrops.
In addition, Betahistine has a powerful antagonistic effect at H3 receptors, and increases the levels of neurotransmitters released from the nerve endings.
Pharmacodynamics: The exact mechanism of action of Betahistine is unclear. However, animal studies have shown that Betahistine improves blood flow in the striae vascularis of the inner ear, resulting in reduced endolymphatic pressure.
Pharmacologic evaluation showed that Betahistine may exert weak H1 receptor agonistic activity and H3 antagonistic properties in the central and autonomic nervous systems. Betahistine also appears to inhibit spike generation of neurons in the lateral and medial vestibular nuclei in a dose-dependent manner.
Pharmacokinetics: Betahistine is rapidly and completely absorbed after oral administration. It is rapidly and almost completely metabolized into 2-pyridylacetic acid (2-PAA), its main metabolite which has no pharmacological activity. Since plasma Betahistine levels are very low, pharmacokinetic analyses are therefore based on 2-PAA measurements in plasma and urine. Peak plasma concentrations of 2-PAA achieved one hour after oral administration in fasting subjects and declines with a half-life of about 3.5 hours. Tissue distribution of Betahistine in humans is unknown. The drug has little or no binding to either serum albumin, or other plasma proteins.
It is not known to what extent the drug crosses the placenta. The effects of hepatic and renal disease on the kinetics of Betahistine are unknown.
Betahistine is eliminated in the kidney with 85 to 90% of the radioactivity of an 8 mg dose appearing in the urine over 56 hours. The maximum rates of excretion are reached within 2 hours of administration. The drug is excreted in the urine as 2-PAA with no unchanged Betahistine being detected.