EFFECTS OF MK-801 (DIZOCILPINE) AND KETAMINE ON STRYCHNINE-INDUCED CONVULSIONS IN RATS - COMPARISON WITH BENZODIAZEPINES AND STANDARD ANTICONVULSANTS

The effects of two non-competitive NMDA antagonists - MK-801 and ketam ine - were studied in a model of generalized seizures elicited by s.c. injection of strychnine (2 or 3 mg/kg) in adult rats. The animals wer e observed in isolation for 30 min after strychnine administration. Pr etreatment with MK-801 (0.5 or 2 mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized seizures following both doses of strychnine. A similar action of ketamine (20 or 40 mg/kg i.p.) was ind icated but it did not attain statistical significance. Strychnine-indu ced lethality was not changed significantly. A comparison with antiepi leptic drugs demonstrated that only phenobarbital (10-80 mg/kg i.p.) w as clearly effective against strychnine-induced seizures; carbamazepin e (25 or 50 mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) wer e able to suppress the incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the benzodiazepines bretazenil (0.1 or 1 mg/ kg i.p.) and midazolam (two lower doses of 0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of midazolam was partly e ffective. Only phenobarbital, carbamazepine and the highest dose of mi dazolam prevented strychnine-induced lethality.