Review: PDF OnlyMessenheimer John A.Clinical Neuropharmacology: December 1994 - p 548-559 Buy Abstract Summary Lamotrigine (LTG) is a novel anticonvulsant that is potent in the maximal electroshock animal model, indicating efficacy in partial and generalized tonic–clonic seizures. LTG exhibits excellent pharmacokinetic properties: low protein binding (55%), linear metabolism primarily by glucuronidation, an absence of enzyme induction, and a long half-life (25.4 h). One defined mechanism of action is the inhibition of glutamate and aspartate release by a blocking effect on use-dependent voltage sensitive sodium channels. Spontaneous glutamate release is not affected. Over an extensive series of clinical trials involving highly refractory adult patients with partial seizures, LTG has shown statistically significant reduction in mean seizure frequency, with 20–30% of patients achieving at least a 50% reduction in seizures. Perhaps more importantly, LTG has been associated with an improvement in behavior that appears to be related to an effect on the severity of seizures that can be independent of a reduction in seizure frequency. LTG is very well tolerated, the most serious side effect being rash, which led to withdrawal of the medication in 2% of patients enrolled in clinical trials. © Williams & Wilkins 1994. All Rights Reserved.