Effects of betahistine metabolites on frog ampullar receptors

Previous studies have demonstrated that betahistine, an histamine-like subs tance used widely as an anti-vertigo drug, can decrease ampullar receptor r esting discharge without affecting their mechanically evoked responses. Pha rmacokinetic studies have shown that this drug is transformed, mainly at th e hepatic level, into aminoethylpyridine (M-1), hydroxyethylpyridine (M-2), then excreted with the urine as pyridylacetic acid (M-3). The goal of the present study was to investigate whether betahistine metabolites are also a ble to affect vestibular receptor activity. Results demonstrated that, in t he range tested (10(-7)-10(-2) M), M-2 and M-3 exerted no effect, whereas M -1, at concentrations higher than 10(-6) M, was able to reduce the resting discharge of ampullar receptors without affecting the evoked responses. M-1 therefore exerts effects similar to those of betahistine on ampullar recep tors. This might be of some clinical interest. On the basis of our data, th e hypothesis may be put forward that the anti-vertigo action of betahistine is at first achieved by betahistine itself and then sustained by M-1.