Studies on the blocking action of 2‐(4‐phenyl piperidino) cyclohexanol (AH5183)

Abstract

1 . AH5183 (2-(4-phenyl piperidino) cyclohexanol) produced neuromuscular block of slow onset in rapidly stimulated nerve-skeletal muscle preparations of the rat, chicken and cat. 2 . The neuromuscular block was not antagonized by neostigmine, tetraethylammonium (TEA) or choline. The rate of onset of transmission failure was enhanced by factors which increase the release of acetylcholine. 3 . It was concluded that the neuromuscular blocking activity was primarily pre-junctional in origin, being due either to a non-competitive action on the choline transport mechanism, or to an intracellular action on acetylcholine metabolism. 4 . In high doses AH5183 possessed local anaesthetic activity, but this was considered insufficient to bring about the failure of neuromuscular transmission. 5 . AH5183 also produced a block of sympathetically innervated preparations that was indistinguishable from that produced by an α-adrenoceptor blocking drug.