ACTIONS OF VESAMICOL ON AN ALPHA-BUNGAROTOXIN-SENSITIVE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR

Electrophysiology and binding studies were used to determine the actio ns of vesamicol [2-(4-phenylpiperidino)cyclohexanol, (AH5183)] on an a lpha-bungarotoxin-sensitive, neuronal nicotinic acetylcholine receptor in the nervous system of the cockroach, Periplaneta americana. Electr ophysiological studies on an identified motor neurone revealed a rever sible blocking action of (+/-)-vesamicol on the response to ionophoret ically applied acetylcholine with an IC50 value of 8.0 X 10(-6) moll-1 . The block was weakly voltage-dependent over the membrane potential r ange of -50 mV to -90 mV, and appeared to be non-competitive. No diffe rence in potency was observed between the resolved stereoisomers, (+/- )-Vesamicol was found to suppress specific binding of I-125-labelled a lpha-bungarotoxin to cockroach nervous tissue with an IC50 value of 5. 1 X 10(-3) mol l-1 and an estimated Hill coefficient of 0.73. Differen ces in the Hill coefficients were found when the resolved stereoisomer s were tested separately. These data provide the first demonstration o f a blocking action by vesamicol of a neuronal nicotinic acetylcholine receptor.