Actions of a series of bisquaternary compounds on nicotinic acetylcholine receptors in insects: ligand binding and electrophysiological studies.

A series of bisquaternary ammoniums, with chain lengths of between 4-12 carbon atoms (C4-C12), have been tested for their ability to block acetylcholine-induced responses in the fast coxal depressor motor neurone (Df) of the cockroach (Periplaneta americana) and to displace [125I]alpha-bungarotoxin from membrane preparations of the CNS of the cockroach. The physiological studies showed that tetramethonium was inactive, whereas hexa-, octa- and dodecamethonium showed an enhanced ability to block acetylcholine-induced responses as the chain length increased. Decamethonium resulted in a slight increase in acetylcholine-induced depolarizations. Ligand binding studies showed that the ability of the compounds to inhibit the specific binding of [125I]alpha-bungarotoxin increased with size from C4-C12. The results show that neuronal nicotinic receptors in insects differ in aspects of their pharmacology from both the major subclasses of nicotinic receptors of vertebrates.