LAMOTRIGINE INHIBITS MONOAMINE UPTAKE IN-VITRO AND MODULATES 5-HYDROXYTRYPTAMINE UPTAKE IN RATS

Lamotrigine is a novel anticonvulsant drug which also stabilises mood in bipolar illness via an unknown mechanism. We report the concentrati on-dependent inhibition of 5-hydroxytryptamine (5-HT) uptake in both h uman platelets and rat brain synaptosomes (IC50 were 240 and 474 mu M, respectively) by lamotrigine. Synaptosomal uptake of noradrenaline (I C50 239 mu M) and dopamine (IC50 322 mu M) was also inhibited. Tetrodo toxin failed to modulate 5-HT uptake suggesting that sodium channel bl ockade does not mediate the lamotrigine effect. Lithium, sodium valpro ate, zonisamide, and carbamazepine all possess anti-manic activity but only the latter inhibited 5-HT uptake. The inhibition of the p-chloro amphetamine-induced 5-HT syndrome in rats suggests that lamotrigine al so inhibits 5-HT uptake in vivo. These effects probably reflect an aff inity for biogenic amine transporters. However, at present, it remains uncertain whether, at clinically effective doses, these effects contr ibute significantly to the efficacy of lamotrigine in bipolar illness. (C) 1998 Elsevier Science B.V. All rights reserved.