Merislon Mechanism of Action

Merislon dilates pre-capillary sphincters, increasing the blood flow in the inner ear. It controls the permeability of capillaries in the inner ear, thereby removes endolymphatic hydrops. It also improves cerebral circulation, increasing blood flow in the internal carotid artery. Thus, Merislon is clinically useful for the relief of vertigo and dizziness.
Pharmacology: Improvement of Circulatory Disturbances in the Inner Ear: In experiments in which microcirculation disturbances were induced in the inner ear of the guinea pig, the blood flow increased to 148% of the control level within 30 min after the intraperitoneal injection of betahistine mesylate. This effect was specific for pathological conditions.
Removal of Endolymphatic Hydrops of the Inner Ear: The lymph flow through the thoracic duct of an anesthetized dog transiently increased 2-3.5 times after the IV injection of betahistine mesylate. The results are interpreted to indicate that the endolymphatic hydrops were excreted as lymph.
With respect to blood flow in the inner ear of a guinea pig that was administered betahistine mesylate, the static level of the inner ear pressure decreased and the pulse wave was amplified. The findings suggest that Merislon increases blood flow in the inner ear and stimulates the excretion and absorption of inner ear fluid.
Improvement of Intracerebral Blood Flow: Betahistine mesylate induced >50% increase in blood flow through the internal carotid artery of anesthetized dogs. This effect was not antagonized by pre-treatment with antihistaminics; rather, it was intensified.
Clinical Studies: Clinical Efficacy: In clinical trials, including double-blind studies, treatment of a total of 875 patients confirmed that Merislon is effective and useful in relieving vertigo and dizziness associated with Meniere's disease, Meniere's syndrome or peripheral vertigo.
Adverse Reactions: Of 2254 patients treated with Merislon, adverse reactions were reported in 26 cases (1.2%). The most common adverse reactions were nausea in 10 patients (0.4%) and eruption in 3 patients (0.1%).
Effects on Laboratory Values: With respect to laboratory test values, no changes attributable to Merislon treatment have been observed.
Pharmacokinetics: Animal Studies: Absorption, Distribution and Excretion: In male beagles of about 10 kg body weight given a single oral 240-mg dose of betahistine mesylate, the peak plasma concentration occurred 60-90 min after administration, after which betahistine mesylate rapidly disappeared from the plasma.
In rats administered H³-labelled betahistine mesylate in doses of 5-6 mg/kg, the highest concentrations of radioactivity were observed in the liver, and then in the fatty tissue, spleen and kidneys. Approximately 10-30% and 50-70% of the administered radioactivity were recovered in the urine and in the feces, respectively, within the first 24 hrs after administration.
Toxicology: Acute Toxicity LD₅₀ (mg/kg): See table.

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Subacute and Chronic Toxicity: Betahistine mesylate was orally administered to both sexes of Wistar-strain rats, in doses of 13, 39, 117 and 350 mg/kg/day, consecutively for 3 months, and doses of 13, 39, 117 and 350 mg/kg/day for 6 months. No abnormalities were found in weight gain, general condition, hematological and clinico-biochemical examinations, nor urine tests. Histopathological examinations revealed blood congestion in the spleen and atrophy of lymphatic nodules in the group of animals receiving the 3-month administration of the 117 and 350 mg/kg/day doses.
Reproduction Studies: No evidence of dysmorphogenic effects on the offspring nor effects on postnatal development were observed in reproduction studies of pregnant rats of about 200 g body weight given 50-2000 mg/kg/day of betahistine mesylate on days 9 through 14 of gestation; however, there was a slight increase in the frequency of dead embryos at the highest dose level of 2000 mg/kg/day.
Treatment of pregnant mice of about 20 g body weight with betahistine mesylate, at doses of 50, 500 and 2500 mg/kg/day, for 2-3 consecutive days beginning on day 7 of gestation caused dead embryos, abnormal neural arches of cervical vertebrae, and lack of the 14th rib (highest dosage), asymmetric and slightly reduced numbers of sternal ossification nuclei, supernumerary phalanx media and incompletely ossified ankle and heel bones (mid-range dosage).