An investigation on the mechanism of anticonvulsant action of ketamine and phencyclidine on convulsions due to cortical application of penicillin in rabbits.

The intracortical injection of 500 units of penicillin in rabbits elicited intermittent bilateral spikes or spike-wave complexes followed by generalization of the epileptiform activity characterized by repeated ictal high-voltage, high frequency spikes paralleled by generalized convulsions. Administration of phencyclidine (PCP) (0.7-1.0 mg/Kg i.v.), ketamine (KT) (20-40 mg/Kg i.v.), pentobarbital (PB) (10 mg/Kg i.v.) and diazepam (3 mg/Kg i.v.) inhibited the generalization of the epileptiform activity induced by penicillin (500 units) counteracting the EEG and motor patterns of the ictal events, while did not influence the interictal spike-and-wave complexes. Physostigmine (0.1 mg/Kg i.v.), clonidine (0.1 mg/Kg i.v.), haloperidol (1 mg/Kg i.v.) and naloxone (10 mg/Kg i.v.) did not affect the inhibitory influence of PCP on epileptiform activity due to cortical application of penicillin. Thus, the mechanism of this anticonvulsant action of PCP seems not to depend on the neurotransmitter system related to the reported drugs. The mechanism of action of PCP and KT is discussed in connexion with the similarities of the effects of this drugs in respect to sigma opiate agonists and pentobarbital.