The dissociative anesthetic phencyclidine (PCP) is a powerful anticonvulsant in a variety of animal seizure models. This activity is in part due to PCP's action as an noncompetitive (open channel) NMDA antagonist. However, PCP is an effective anticonvulsant in certain seizure models where other NMDA antagonists (such as dizocilpine) are inactive. Moreover, PCP produces a variety of side effects, some of which are not shared by other NMDA receptor antagonists. In whole cell voltage-clamp recordings, PCP was a potent blocker of N-type Ca2+ channels in acutely isolated guinea-pig CA 1 hippocampal neurons. The block appeared to occur by binding of the drug to an activated state of the Ca2 + channel that is distinct from the open state. This use-dependent block of Ca2 + channels may contribute to PCP's anticonvulsant activity in some seizure models and may account for certain of PCP's unique behavioral actions, particularly those not shared by dissociative anesthetic-like compounds such as ketamine and dizocilpine which were only weak Ca2 + channel antagonists.
