SIMILAR POTENCY OF CARBAMAZEPINE, OXCARBAZEPINE, AND LAMOTRIGINE IN INHIBITING THE RELEASE OF GLUTAMATE AND OTHER NEUROTRANSMITTERS

被引:112
作者
WALDMEIER, PC
BAUMANN, PA
WICKI, P
FELDTRAUER, JJ
STIERLIN, C
SCHMUTZ, M
机构
[1] Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel
关键词
D O I
10.1212/WNL.45.10.1907
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We compared the effects of the antiepileptic drugs carbamazepine, oxcarbazepine, and lamotrigine on the release from rat brain slices of endogenous glutamate, [H-3]-GABA, and [H-3]-dopamine, elicited by the Na+ channel opener, veratrine, and of the same transmitters as well as [H-3]-noradrenaline, [H-3]-5-hydroxytryptamine, and [H-3]-acetylcholine, elicited by electrical stimulation. The three antiepileptic drugs inhibited veratrine-induced release of endogenous glutamate, [H-3]-GABA, and [H-3]-dopamine, with IC50 values between 23 and 150 mu M, in or near the concentration range in which they interact with Na+ channels, and there was little difference between the compounds. They were five to seven times less potent in inhibiting electrically as compared with veratrine-stimulated release of [H-3]-GABA and [H-3]-dopamine; similarly, carbamazepine and tetrodotoxin were more potent in inhibiting veratrine-induced as compared with electrically induced release of endogenous glutamate. Carbamazepine, oxcarbazepine, and lamotrigine also inhibited electrically stimulated release of [H-3]-5-hydroxytryptamine (IC50 values, 150 to 250 mu M) and [H-3]-acetylcholine (IC50 values, 50 to 150 mu M); [H-3]-noradrenaline release was affected to a lesser degree. The active concentration ranges of these drugs with respect to inhibition of veratrine-stimulated neurotransmitter release matched the therapeutic plasma and brain concentrations. It is uncertain whether these effects are relevant in vivo at anticonvulsant doses, because the drugs are markedly less potent in inhibiting the more physiologic release elicited by electrical stimulation. Therefore, the hypothesis that inhibition of glutamate release is the mechanism of anticonvulsant action of lamotrigine (or carbamazepine and oxcarbazepine) is doubtful. Other consequences of Na+ channel blockade may have an important role.
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页码:1907 / 1913
页数:7
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