The effects of phenytoin and phenobarbital on seizures induced by imipenem/cilastatin in rats.

The effects of phenytoin (PHT) and phenobarbital (PHB) on EEG activity and behavior was studied in the model of epilepsy induced by intracerebroventricular (i.c.v.) administration of imipenem/cilastatin (Imi/Cil). Under intraperitoneal (i.p.) sodium pentobarbital anesthesia adult male Wistar albino rats were implanted with electrodes and cannulas were placed into the right lateral ventricle. Animals were divided into groups: 1) Imi/Cil (100/100 microg, i.c.v.), 2) PHT (40 mg/kg) + Imi/Cil (100/100 microg, i.c.v), 3) PHT (80 mg/kg) + Imi/Cil (100/100 microg, i.c.v.), 4) PHT (160 mg/kg) + Imi/Cil (100/100 microg, i.c.v.), 5) PHB (50 mg/kg) + Imi/Cil (100/100 microg, i.c.v.), and 6) PHB (80 mg/kg) + Imi/Cil (100/100 microg, i.c.v.). PHT and PHB were injected intraperitoneally (i.p.) 1 h before Imi/Cil. Seizures were scored according to the scale: 0--normal behavior; 1--twitching, 2--head nodding, forelimb clonus, 3--rearing, and 4--clonic-tonic convulsions. Imi/Cil provoked maximal seizures in all animals, and all rats died 10 - 18 min after the injection. Epileptiform activity preceded behavioral seizures. Clonic-tonic seizures were associated with continuous bursts of high-frequency high-amplitude spikes in the EEG. PHT and PHB suppressed Imi/Cil-induced seizures dose-dependently. PHB reduced epileptiform discharges during behavioral seizures elicited by Imi/Cil, while PHT had no effect on EEG epileptic phenomena. These results suggest that PHT acts as anticonvulsant, and PHB as anticonvulsant and antiepileptic agent in the model of epilepsy induced by Imi/Cil.