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

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 alpha-adrenoceptor blocking drug.