Betahistine produces post-synaptic inhibition of the excitability of the primary afferent neurons in the vestibular endorgans

Betahistine has been used to treat several vestibular disorders of both cen tral and peripheral origin. The objective of this work was to study the act ion of betahistine in the vestibular endorgans. Experiments were done in wi ld larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode, Betahistine (10 muM to 10 mM; n = 32) inhibited the basal spike discharge o f the vestibular afferent neurons with an IC50 of 600 muM. To define the si te of action of betahistine, its interactions with the nitric oxide synthas e inhibitor N-G-nitro-L-arginine (3 muM) and with the cholinergic antagonis ts atropine (10 muM; n = 3) and d-tubocurarine (10 muM; n = 3) were studied . The action of betahistine when co-administered with these drugs was the s ame as that in control experiments, indicating that its effects did not inc lude nitric oxide production or the activation of cholinergic receptors. In contrast, 0.01-1 mM betahistine reduced the excitatory action of kainic ac id (10 muM; n = 6) and quiscualic acid (I muM; n = 13) These results indica te that the action of betahistine on the spike discharge of afferent neuron s seems to be due to a post-synaptic inhibitory action on the primary affer ent neuron response to the hair cell neurotransmitter.