Otsuki K, Morimoto K, Sato K, Yamada N, Kuroda S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Epilepsy Res. 1998 Jul;31(2):101-12. doi: 10.1016/s0920-1211(98)00018-7.
We investigated the anticonvulsant and adverse behavioral effects of lamotrigine (LTG), a novel antiepileptic drug (AED), as well as other conventional AEDs on kindled seizures in rats. We also applied an anticonvulsive dose of LTG in vivo to rats in which the hippocampus had been subjected to long-term potentiation (LTP). LTG potently attenuated limbic-kindled seizures in a dose-dependent fashion, at doses at which animals showed no adverse behavioral effects. LTG was effective in preventing kindled seizures for up to 24 h after a single i.p. administration. The anticonvulsant effects of LTG were reversed when the stimulus current was raised to two or three times the generalized seizure-triggering threshold. Among the AEDs examined, valproate and LTG were the only drugs that engendered a potent anticonvulsant effect without concomitant adverse behavioral effects. Although all of the other AEDs exhibited anticonvulsant effects with various potencies, they produced adverse effects such as sedation or motor ataxia. Furthermore, an anticonvulsant dose of LTG did not affect either the induction or maintenance of tetanus-induced LTP in the hippocampus. These results indicate that LTG potently suppresses limbic-kindled seizures by raising the seizure triggering-threshold in the kindling focus at doses that do not affect LTP in the hippocampus.
我们研究了新型抗癫痫药物（AED）拉莫三嗪（LTG）以及其他传统AED对大鼠点燃性癫痫发作的抗惊厥作用和不良行为影响。我们还对海马经历了长期增强（LTP）的大鼠进行了体内抗惊厥剂量的LTG给药。LTG以剂量依赖性方式有效减轻边缘叶点燃性癫痫发作，且在该剂量下动物未表现出不良行为影响。单次腹腔注射后，LTG在长达24小时内有效预防点燃性癫痫发作。当刺激电流提高到全身性癫痫发作触发阈值的两倍或三倍时，LTG的抗惊厥作用被逆转。在所研究的AED中，丙戊酸盐和LTG是仅有的两种产生有效抗惊厥作用且无伴随不良行为影响的药物。尽管所有其他AED均表现出不同程度的抗惊厥作用，但它们会产生诸如镇静或运动性共济失调等不良反应。此外，抗惊厥剂量的LTG对海马中强直刺激诱导的LTP的诱导或维持均无影响。这些结果表明，LTG通过在不影响海马LTP的剂量下提高点燃灶中的癫痫发作触发阈值，有效抑制边缘叶点燃性癫痫发作。
