Abstracts

RATIONALE: Vigabatrin is a widely used antiepileptic drug that greatly increases whole brain ?-aminobutyric acid(GABA). But little is known about the anticonvulsant effect of vigabatrin on pilocarpine-induced seizures in the immature rats. We sought to determine the effects of vigabatrin on pilocarpine-induced seizures in the immature rats. METHODS:_We classified 6-10 day old Sprague-Dawley rats into control(n=5) and vigabatrin-treated group that were pretreated with 30(n=5), 70(n=5), and 100(n=5)mg/kg of vigabatrin. Animals were received vigabatrin or saline, intraperitonealy for 6 days, once a day. And on 5th day, right and left cortical electrodes were placed in 10-14 day old animals. The following day 2.5-hour EEG recordings were obtained to monitor the latency to first electrographic seizures and to status epilepticus induced by intraperitoneal injection of pilocarpine (200mg/kg). Data were analyzed using the log-rank test. RESULTS: The electrographic seizure and status epilepticus were seen in 80%(n=4) of rats pretreated with 30mg/kg of vigabatrin, and in 100% of control rats. But we had to discontinue the pretreatment with 70 and 100mg/kg of vigabatrin, because the rats were noted decreases in body weight gain and behavior change such as sluggish movement and an apathy to surroundings starting with the 3rd day of pretreatment and persisting throughout the study, even a rat that received 100mg/kg of vigabatrin died during status epilepticus after pilocarpine injection. And the latency to first seizure was 20.5?5.2 minutes in 30mg/kg of vigabatrin group and 8.8?2.0 minutes in control (p<0.02) and to status epilepticus was 29.3?6.3 minutes in 30mg/kg of vigabatrin group and 12.2?1.2 minutes in control(p<0.03). CONCLUSIONS: We confirmed that 30mg/kg of vigabatrin adminstration for 6 days does not affect the body weight gain and behavior of the immature rats and has an anticonvulsant effect. These findings might demonstrate that the prolonged latency to seizure and to status epilepticus is a time to reduce GABA level that were elevated in the brain by vigabatrin administration below the seizure threshold by pilocarpine.