Anticonvulsant actions of phencyclidine receptor ligands: correlation with N-methylaspartate antagonism in vivo.

1. Drugs with phencyclidine (PCP)-like activity in behavioural discrimination and [3H]PCP binding studies share anticonvulsant properties. 2. We have compared the rank order potency of a series of PCP-like compounds as N-methylaspartate (NMA) antagonists, determined from previously published studies from our laboratory, with their rank order anticonvulsant potencies as determined by two independent research groups in three different in vivo models of experimentally-induced epilepsy. 3. Rank order potency for NMA antagonism correlated well with rank order anticonvulsant potency. Furthermore, the systemic doses required for an effective blockade of NMA-evoked excitations were, in most cases, similar to those which produced anticonvulsant activity. 4. The results suggest that functional NMA antagonism may underlie the shared anticonvulsant properties of structurally dissimilar compounds with PCP-like activity.