Comparison between the effect of propofol and midazolam on picrotoxin-induced convulsions in rat

Propofol is a short acting intravenous anesthetic that has been used in the treatment of status epileptics. However, the occurrence of seizures in epileptic and non-epileptic patients during recovery from propofol induced anesthesia suggests that propofol may have proconvulsant effects. We have previously shown that propofol displays anticonvulsant effects against picrotoxin (PTX) induced seizures during its peak sedative effects. The purpose of the present study was to compare the time course of the effect of intravenous administration of various doses (2.5, 5, and 10 mg/kg) of propofol and midazolam on PTX-induced seizures in adult female Sprague-Dawley rats. The latency to onset of clonic seizures induced by intraperitoneal injection of PTX was significantly increased by the highest dose of propofol and all doses of midazolam, suggesting that both agents display anticonvulsant effects. The anticonvulsant effects of propofol (10 mg/kg) lasted about 20 min and PTX-induced clonic seizures were observed thereafter and peaked within 30 min post drug administration. Clonic seizures progressed rapidly to tonic seizures leading to high rate of PTX-induced mortality. In midazolam (10 mg/kg) treated rats, clonic seizures were observed 25 min after drug administration and the number of rats exhibiting clonic seizures was highest within 40 min. However, clonic seizures did not progress into tonic seizures and thus, PTX-induced seizure related mortality was significantly reduced. In conclusion, this study provides further evidence for the anticonvulsant effects of propofol and midazolam against PTX-induced seizures. Furthermore, the data of the current study showed that midazolam was more effective than propofol against PTX-induced tonic seizures.