The narcotic antagonist naltrexone has a biphasic effect on the nicotinic acetylcholine receptor

It is known that narcotic antagonists interact with many cholinergic pathways but less in known about specific mechanisms. Using neonatal rat myoballs to study single channel behaviour of the acetylcholinegated nicotinic receptor, it was found that micromolar concentrations of naltrexone had no effect on channel conductance but caused open channel blockade by increasing the flickering from the open to the closed state in a concentration-dependent manner. At micromolar concentrations of naltrexone, the frequency of channel opening was decreased and bursts were grouped in clusters, whereas at nanomolar levels the frequency of opening was increased. The sequential model for ion-channel blockade cannot explain these effects, and an alternative allosteric mechanism of action is proposed.