A CALCIUM ANTAGONISTIC EFFECT OF THE NEW ANTIEPILEPTIC DRUG LAMOTRIGINE

The new antiepileptic drug lamotrigine (LTG; 3,5-diamino-6-(2,3-dichlo rophenyl)-1,2,4-triazine) has been shown to be effective in the treatm ent of focal epilepsies with or without secondary generalization. Furt hermore, some case reports indicate an efficacy in the treatment of bi polar affective disorders. It has been suggested that the main mechani sm of action of LTG is the inhibition of glutamate release through blo ckade of voltage sensitive sodium channels and stabilisation of the ne uronal membrane. Since some antidepressant drugs and the antiepileptic substance carbamazepine have calcium antagonistic properties, which m ay be of significance in the pathophysiology of epilepsies and affecti ve disorders, the interaction of lamotrigine with carbamazepine and th e organic calcium channel blocker verapamil was analyzed in the low Mg 2+-induced model epilepsy which has been shown to be suppressed specif ically by organic calcium antagonists. Lamotrigine reduced the frequen cy of occurrence of low-magnesium induced field potentials in CAI and CA3 areas of the hippocampus slice preparation (guinea pigs) in a dose -dependent manner. The subthreshold concentrations which yielded no ef fect were 1 mu mol/l for lamotrigine, 10 mu mol/l for carbamazepine an d 2 mu mol/l for verapamil. Combinations of these subthreshold concent rations elicited a reduction in the repetition rate of field potential s. The results indicate that lamotrigine behaves additive with verapam il and carbamazepine what can be due to a common action on the same su btype of calcium channels. It can be assumed that lamotrigine may have besides its action on high-frequency sodium dependent action potentia ls also effects on calcium channels. (C) 1997 Elsevier Science B.V.