Nuvert Mechanism of Action

Pharmacology: Pharmacodynamics: The mechanism of action of betahistine is known partially. Betahistine has a very strong affinity as an antagonist for histamine H3 receptors and a weak affinity as an agonist for histamine H 1 receptors. Betahistine has two modes of action. Primarily, it has a direct stimulating (agonistic) effect on H1 receptors located on blood vessels in the inner ear. It appears to act on the precapillary sphincter in the stria vascularis of the inner ear, thus reducing the pressure in the endolymphatic space.
In addition, betahistine has a powerful antagonistic effects at H3 receptors, and increases the levels of neurotransmitters released from the nerve endings. The increased amounts of histamine released from histaminergic nerve endings stimulates H1 receptors, thus augmenting the direct agonist ic effects of betahistine on these receptors. This explains the potent vasodilatory effects of betahistine in the inner ear. This explains the efficacy of betahistine in the treatment of vertigo. Taken together these properties contribute to its therapeutic benefits in Meniere's syndrome. Meniere's syndrome is characterised by attack of vertigo, tinnitus, nausea, headache, hearing loss. The efficacy of betahistine may be due to its ability to modify the circulation of the inner ear or due to a direct effect on neurons of the vestibular nucleus.
Pharmacokinetics: In man, orally administered doses of betahistine hydrochloride are rapidly and completely absorbed from the gastrointestinal tract. The drug is rapidly metabolized to one major metabolite - 2-pyridylacetic acid - and excreted in the urine. Studies with radiolabelled betahistine have demonstrated a plasma half life of 3.4 hours and a urinary half life of 3.5 hours for the radio-label. Urinary excretion of the label was about 90% complete within 24 hours of administration.
Absorption: Betahistine is completely absorbed after oral administration, and peak plasma concentrations of C-labelled betahistine are attained after approximately one hour of oral administration for fasting subjects.
Distribution: Little or no binding occurs with human plasma proteins.
Metabolism and Elimination: Elimination of betahistine takes place mainly by metabolism and the metabolites are subsequently eliminated mainly by renal excretion. Following the absorption, the drug is metabolized rapidly in the metabolite and almost completely in metabolite 2-pyridylacetic acid. After oral administration of betahistine, its plasma levels are very low. Therefore, the assessment of the pharmacokinetics of betahistine is based on the plasma concentration data of the only metabolite 2-pyridylacetic acid. The concentration of 2-pyridylacetic acid reaches its maximum at I hour after intake and declines with half approximately 3.5 hours. The 2-pyridylacetic acid easily excreted in urine. In the dose range between 8 and 48 mg, about 85% of the original dose was recovered in the urine.85-90% of the radioactivity of an 8 mg dose appears in the urine over 56 hours, with maximum excretion rates reached within 2 hours of administration. There is no evidence of presystemic metabolism and biliary excretion is not thought to be an important route of elimination for the drug or any of its metabolites. However betahistine is subject to metabolism in the liver.