LAMOTRIGINE VS PHENYTOIN FOR TREATMENT OF STATUS EPILEPTICUS - COMPARISON IN AN EXPERIMENTAL-MODEL

The newly introduced antiepileptic drug, lamotrigine, has been reporte d to have a mechanism of action similar to that of phenytoin. Because phenytoin is a standard clinical treatment for convulsive status epile pticus, we compared the efficacy of lamotrigine to that of phenytoin i n a model of secondarily generalized convulsive status epilepticus in rats that responds to drug concentrations similar to those that have b een reported to be clinically useful for this purpose, Status epilepti cus was induced in rats with actively epileptogenic cortical cobalt le sions by administration of homocysteine thiolactone. While phenytoin-c ontrolled generalized tonic clonic seizures in this model with a media n effective dose of 100.5 mg/kg (16.0 mu g/ml in serum), lamotrigine w as ineffective at doses ranging from 10 to 100 mg/kg, with serum drug concentrations (2.5-43.5 mu g/ml) within or above the reported 'therap eutic' concentration for LTG treatment of chronic epilepsy. Lamotrigin e also failed to prevent the onset of generalized tonic clonic seizure s when given prior to homocysteine, while phenytoin was effective in t his test. Studies of lamotrigine kinetics in serum and brain revealed that the drug was well-absorbed following i.p. injection and that it e ntered brain rapidly enough to have exerted an anti-status effect in t hese experiments. These results suggest that lamotrigine and phenytoin have differences in their mechanisms of anticonvulsant action, leadin g to very different abilities to control status epilepticus.