Betahistine is widely used in the treatment of peripheral and central vestibular disorders. Till now the anti-vertigo effect of the drug was though to be mainly due to an action of betahistine on inner ear or cerebral microcirculation or on some structures of the CNS, chiefly the vestibular nuclei. Vertigo, however is, in most cases, of peripheral origin but it remains unknown whether betahistine, or some of its metabolities, may directly affect the vestibular system at peripheral level. Pharmacokinetic studies have in fact demonstrated that betahistine is transformed, mainly at the hepatic level, in aminoethylpyridine (M1), hydroxyethylpyridine (M2) and, finally, in pyridylacetic acid (M3) which is excreted with the urine. All these substances are therefore present in the body fluids of subjects treated with betahistine, and thus might have pharmacological effects. The goal of the present study was to investigate whether betahistine or some of its metabolites could exert any effect on vestibular receptors. To this end, the effects of the drugs (10(-7)-10(-2) M) have been examined on frog semicircular canals, an animal model well suited for this purpose. The effects of betahistine and of its metabolites have been evaluated by recording ampullar receptor activity both at rest and during mechanical stimulation of the sensory organ. The results demonstrated that both betahistine and one of its metabolites, the aminoethylpyridine (M1), exert effects quite similar on ampullar receptors; both these substances in fact could reduce greatly ampullar receptor resting discharge but had scanty effects on mechanically-evoked responses. This observation might justify betahistine and possibly M1 anti-vertigo effects. In fact vertigo is normally due to uncontrolled changes in vestibular receptor resting discharge. It is therefore probable that any factor able to reduce vestibular receptor resting firing rate and, in consequence, its variations, may have, as final effect, an anti-vertigo action. The observation that betahistine and M1 have similar effects might be of some clinical interest. In fact, on the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained and prolonged in time by M1.

Effects of Betahistine and of its metabolites on vestibular sensory organs

BOTTA, LAURA;MIRA, EUGENIO;ZUCCA, GIANPIERO;VALLI, PAOLO
2001

Abstract

Betahistine is widely used in the treatment of peripheral and central vestibular disorders. Till now the anti-vertigo effect of the drug was though to be mainly due to an action of betahistine on inner ear or cerebral microcirculation or on some structures of the CNS, chiefly the vestibular nuclei. Vertigo, however is, in most cases, of peripheral origin but it remains unknown whether betahistine, or some of its metabolities, may directly affect the vestibular system at peripheral level. Pharmacokinetic studies have in fact demonstrated that betahistine is transformed, mainly at the hepatic level, in aminoethylpyridine (M1), hydroxyethylpyridine (M2) and, finally, in pyridylacetic acid (M3) which is excreted with the urine. All these substances are therefore present in the body fluids of subjects treated with betahistine, and thus might have pharmacological effects. The goal of the present study was to investigate whether betahistine or some of its metabolites could exert any effect on vestibular receptors. To this end, the effects of the drugs (10(-7)-10(-2) M) have been examined on frog semicircular canals, an animal model well suited for this purpose. The effects of betahistine and of its metabolites have been evaluated by recording ampullar receptor activity both at rest and during mechanical stimulation of the sensory organ. The results demonstrated that both betahistine and one of its metabolites, the aminoethylpyridine (M1), exert effects quite similar on ampullar receptors; both these substances in fact could reduce greatly ampullar receptor resting discharge but had scanty effects on mechanically-evoked responses. This observation might justify betahistine and possibly M1 anti-vertigo effects. In fact vertigo is normally due to uncontrolled changes in vestibular receptor resting discharge. It is therefore probable that any factor able to reduce vestibular receptor resting firing rate and, in consequence, its variations, may have, as final effect, an anti-vertigo action. The observation that betahistine and M1 have similar effects might be of some clinical interest. In fact, on the basis of our data, the hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained and prolonged in time by M1.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/103540
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