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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Carbamazepine inhibits distinct chemoconvulsant-induced seizure-like activity in Dugesia tigrina.
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Carbamazepine inhibits distinct chemoconvulsant-induced seizure-like activity in Dugesia tigrina.

机译：卡马西平抑制tigug豚鼠化学惊厥诱导的癫痫样发作活动。

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Planaria, non-parasitic flatworms, were recently shown to be a simple yet sensitive model for investigating the pharmacology of convulsants and anticonvulsants. The present findings show that three distinct chemoconvulsants, (-)-nicotine, picrotoxin, and N-methyl-D-aspartate (NMDA), induce dose-dependent seizure-like paroxysms in the planarian Dugesia tigrina. Carbamazepine and oxcarbazepine, iminodibenzyl derivatives, exhibit anticonvulsive effects mediated mainly through the inactivation of voltage-gated sodium channels. Apart from these primary molecular targets, both carbamazepine and oxcarbazepine are known to activate gamma-aminobutyric acid type A (GABA(A)) receptors and inhibit NMDA activated glutamate receptors and neuronal nicotinic acetylcholine receptors (nAChRs). The present study shows that in D. tigrina both carbamazepine and oxcarbazepine inhibit chemoconvulsant-induced seizure behaviors in a dose-dependent manner. Carbamazepine (100 muM) decreased by ~65% the cumulative mean planarian seizure-like activity (pSLA) observed in the presence of (-)-nicotine (10 muM), picrotoxin (5mM), or NMDA (3mM), whereas oxcarbazepine (1 muM) decreased by 45% the cumulative mean pSLA induced by (-)-nicotine (10muM). The results demonstrate, for the first time, the anti-seizure pharmacology of carbamazepine and oxcarbazepine in an invertebrate seizure model.
机译：浮游动物，非寄生虫扁虫，最近被证明是一种简单而敏感的模型，用于研究惊厥药和抗惊厥药的药理作用。目前的发现表明，三种不同的化学惊厥药，（-）-尼古丁，微毒素和N-甲基-D-天门冬氨酸（NMDA）诱导了黄粉虫Dugesia tigrina的剂量依赖性癫痫样发作。亚氨基二苄基衍生物卡马西平和奥卡西平显示出主要通过电压门控钠通道失活介导的抗惊厥作用。除了这些主要的分子靶标外，已知卡马西平和奥卡西平均能激活A型γ-氨基丁酸（GABA（A））受体并抑制NMDA激活的谷氨酸受体和神经元烟碱型乙酰胆碱受体（nAChRs）。本研究表明，在虎杖中，卡马西平和奥卡西平均以剂量依赖性方式抑制化学惊厥引起的癫痫发作。卡马西平（100μM）在（-）-尼古丁（10μM），微毒素（5mM）或NMDA（3mM）存在的情况下观察到的累积平均涡虫样癫痫样活动（pSLA）降低约65％ 1μM）使（-）-尼古丁（10μM）诱导的累积平均pSLA降低了45％。结果首次证明了卡马西平和奥卡西平在无脊椎动物癫痫发作模型中的抗癫痫药理作用。

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