Lamotrigine potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice

Lamotrigine [0.5-10 mg/kg, intraperitoneally (i.p.)] was able to antagonize the audiogenic seizures in DBA/2 mice in a dose-dependent manner. Lamotrigine at doses of 0.5 and 1.25 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, markedly potentiated the anticonvulsant activity of carbamazepine, diazepam, phenytoin, phenobarbital and valproate against sound induced seizures in DBA/2 mice. The degree of potentiation by lamotrigine was greatest for diazepam and valproate, lower for phenobarbital, and least for phenytoin and carbamazepine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of diazepam + lamotrigine or valproate + lamotrigine was more favourable than the diazepam + saline or valproate + saline treatment. Since lamotrigine did not significantly influence the plasma levels of the anticonvulsant drugs studied we might suggest that pharmacokinetic interactions, in terms of total plasma levels, are not probable. However, the possibility that lamotrigine alters protein binding and increases the relative free vs protein bound ratio may not be excluded. Lamotrigine did not significantly affect the hypothermic effects of the anticonvulsant compounds studied. Lamotrigine showed an additive effect when administered in combination with some classical anticonvulsants, most notably valproate and diazepam.