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 central and peripheral origin. The objective of this work was to study the action of betahistine in the vestibular endorgans. Experiments were done in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM; n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 microM) and with the cholinergic antagonists atropine (10 microM; n = 3) and d-tubocurarine (10 microM; n = 3) were studied. The action of betahistine when co-administered with these drugs was the same as that in control experiments, indicating that its effects did not include nitric oxide production or the activation of cholinergic receptors. In contrast, 0.01-1 mM betahistine reduced the excitatory action of kainic acid (10 microM; n = 6) and quiscualic acid (1 microM; n = 13). These results indicate that the action of betahistine on the spike discharge of afferent neurons seems to be due to a post-synaptic inhibitory action on the primary afferent neuron response to the hair cell neurotransmitter.
Soto
E
E
Instituto de Fisiología, Universidad Autónoma de Puebla, Puebla, Mexico. esoto@siu.buap.mx
Chávez
H
H
Valli
P
P
Benvenuti
C
C
Vega
R
R
D000557:Ambystoma; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001621:Betahistine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014722:Vestibule, Labyrinth / Q000166:cytology* / Q000187:drug effects*
D017442:Histamine Agonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D019335:Nitroarginine; D001285:Atropine; D019001:Nitric Oxide Synthase; D014403:Tubocurarine; D001621:Betahistine