A calcium antagonistic effect of the new antiepileptic drug lamotrigine.
The new antiepileptic drug lamotrigine (LTG; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine) has been shown to be effective in the treatment of focal epilepsies with or without secondary generalization. Furthermore, some case reports indicate an efficacy in the treatment of bipolar affective disorders. It has been suggested that the main mechanism of action of LTG is the inhibition of glutamate release through blockade of voltage sensitive sodium channels and stabilisation of the neuronal membrane. Since some antidepressant drugs and the antiepileptic substance carbamazepine have calcium antagonistic properties, which may be of significance in the pathophysiology of epilepsies and affective disorders, the interaction of lamotrigine with carbamazepine and the organic calcium channel blocker verapamil was analyzed in the low Mg(2+)-induced model epilepsy which has been shown to be suppressed specifically by organic calcium antagonists. Lamotrigine reduced the frequency of occurrence of low-magnesium induced field potentials in CA1 and CA3 areas of the hippocampus slice preparation (guinea pigs) in a dose-dependent manner. The subthreshold concentrations which yielded no effect were 1 mumol/l for lamotrigine, 10 mumol/l for carbamazepine and 2 mumol/l for verapamil. Combinations of these subthreshold concentrations elicited a reduction in the repetition rate of field potentials. The results indicate that lamotrigine behaves additive with verapamil and carbamazepine what can be due to a common action on the same subtype of calcium channels. It can be assumed that lamotrigine may have besides its action on high-frequency sodium dependent action potentials also effects on calcium channels.
von Wegerer
J
J
Universität Freiburg, Abt. Psychiatrie und Psychotherapie, Germany.
Hesslinger
B
B
Berger
M
M
Walden
J
J
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D000077213:Lamotrigine; D008564:Membrane Potentials / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014227:Triazines; D000077213:Lamotrigine