Effects of Lamotrigine on Electrically Induced Afterdischarge Duration in Anaesthetised Rat, Dog, and Marmoset

Abstract

The effects of lamotrigine (LTG), a novel potent anticonvulsant, following intravenous (i.v.) bolus injection were studied on the durations of electrically induced afterdischarges of the EEG in halothane-anaesthetised dogs and marmosets, species used in toxicity studies. For comparison, the effect of LTG on hippocampal afterdischarge duration was also studied in halothane anaesthetised rats, a species in which the anticonvulsant action of LTG has been widely investigated. The known anticonvulsants phenytoin (PHT) and phenobarbital (PB) were included for comparison. LTG reduced afterdischarge duration in a dose-dependent manner in rat and dog; it was approximately twofold more potent than PHT in the dog and three- to fourfold more potent than PB in both dog and rat (LTG ED50 values = 4.5 and 11.7 mg .cntdot. kg-1 i.v.). In limited studies in marmosets, i.v. administration of both LTG and PHT (both 5-15 mg .cntdot. kg-1) reduced or abolished afterdischarge. Thus, LTG was a potent anticonvulsant in rat, dog, and marmoset in afterdischarge models of partial (focal) seizures and may be of utility in the treatment of partial seizures in humans.