Anticonvulsant properties of phencyclidine-like drugs in mice

Primarily on the basis of activity in [3H]phencyclidine (PCP) binding assays and drug discrimination studies, a number of structurally dissimilar compounds have been found to be PCP-like. Drugs from four of these classes of PCP-like compounds were examined for anticonvulsant activity in the pentylenetetrazol (PTZ) seizure test. Male albino mice, eight per dose, were administered the drug or vehicle i.p. 10 min before PTZ (125 mg/kg s.c.). At each dose, the number of subjects and latency to clonic and/or tonic seizures within 15 min following PTZ were recorded. The anticonvulsant properties of PCP, ketamine, (+)-N-allylnormetazocine, etoxadrol, dexoxadrol and (-)-2-methyl-3,3-diphenyl-3-propanolamine ((-)-2-MDP) were selective for tonic seizures. The highest dose tested for each compound completely prevented the occurrence of tonic seizures. Levoxadrol and (+)-2-MDP, drugs devoid of PCP-like activity in other tests, were also inactive in the PTZ seizure test. These results demonstrate that similarities among PCP-like drugs previously shown using binding assays and drug discrimination procedures can be extended to include anticonvulsant effects, and they suggest common cellular sites of action for these properties.