Abstract Otology 2000 D04-3

Jan W.C.M. Jansen Ph.D.

Assistant Professor NL-DA Weesp

Betahistine is an orally active compound for the treatment of Ménière's disease and vertigo. The beneficial effect of Betahistine in Ménière's disease is assumed to be caused by increasing inner ear blood flow leading to normalization of the increased osmotic pressure of the endolymph. Animal data support this statement showing increased microcirculation in the inner ear caused by Betahistine administration: Kubicek et al. (1967) measured increased flow changes in labyrinthine arteries in the dog, Suga and Snow (1969) measured an increased blood flow in the cochlea of the guinea pig and Laurikanen et al. (1993) confirmed these phenomena in the rat using laser doppler flowmetry. The H1-agonistic (partial) and the H3-antagonistic properties of Betahistine explain these phenomena. Clear indications are also present that Betahistine affects neuronal activity: Betahistine induces an inhibitory effect on the polysynaptic neurons in the vestibular nuclei. Modulation of the excitability of MVN neurons by the histaminergic system is probably an endogenous mechanism during abnormal vestibular stimulation. Under pathological conditions Betahistine stimulates this mechanism leading to vestibular compensation and conditional improvement : Tighilet et al. (1995) showed that Betahistine treatment strongly accelerated the recovery process of unilateral vestibular neurectomized cats. The H3-antagonistic activity of Betahistine is responsible for this beneficial effect. The observations make clear that 1/ histamine and histamine-receptors play a key role in vestibular processes; 2/ Betahistine affects the vestibular system at different levels: increase of cochlear blood flow and inhibition of vestibular neuronal cell activity leading to accelerated vestibular compensation; 3/ these properties make Betahistine an efficient agent leading to improvement of vestibular dysfunction. Sponsored by: Solvay Pharmaceuticals