VERTI GO E BETAI STI NA. C. BENVENUTI (ED). FORMENTI, MILAN, ITALIA, 2000. 43 Effects of betahistine on the vestibular receptors: binding sites Hortencia Chávez 1,2 , Rosario Vega 1 , Paolo Valli 3 , Eugenio Mira 4 , Claudio Benvenuti 5 , Paul .S. Guth 6 and Enrique Soto 1 1 Instituto de Fisiología, Universidad Autónoma de Puebla, Apartado Postal 406, Puebla, Pue., CP 72000, México. 2 Facultad de Estomatología, Universidad Autónoma de Puebla, 3 Department of Physiological and Pharmacological Sciences, University of Pavia. 4 IRCCS Policlinico S. Matteo, Pavia. 5 Formenti, Milan. 6 Department of Pharmacology and Otolaryngology, Tulane University, New Orleans, USA. Abstract Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work has been to study the betahistine action mechanism at the peripheral level. Experiments were carried out in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 μM to 10 mM, n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC 50 of 600 μM. To study if betahistine action on the afferent nerve discharge was somehow related to nitric oxide (NO) generation, betahistine 1 mM (n = 5) was co-administered with N G -nitro-L-arginine 3 μM. The action of betahistine remained as in control experiments. To determine the influence of betahistine on the efferent innervation of hair cells its interactions with carbachol (200 μM, n = 5), and with cholinergic antagonists: atropine (10 μM, n = 3) and d-tubocurarine (10 μM, n = 3) were also studied. Betahistine 1 mM reduced the excitatory action of carbachol in a 30 ±3.4%. Cholinergic antagonists did not modify betahistine actions. Postsynaptic actions of betahistine were analized on the basis of its capability to interact