Wheatley P L, Miller A A
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, England.
Epilepsia. 1989 Jan-Feb;30(1):34-40. doi: 10.1111/j.1528-1157.1989.tb05277.x.
The effects of lamotrigine (LTG), a novel potent anticonvulsant, following intravenous (i.v.) bolus injection were studied on the durations of electrically induced afterdischarges of the EEG in halothane-anaesthetised dogs and marmosets, species used in toxicity studies. For comparison, the effect of LTG on hippocampal afterdischarge duration was also studied in halothane anaesthetised rats, a species in which the anticonvulsant action of LTG has been widely investigated. The known anticonvulsants phenytoin (PHT) and phenobarbital (PB) were included for comparison. LTG reduced afterdischarge duration in a dose-dependent manner in rat and dog; it was approximately twofold more potent than PHT in the dog and three- to fourfold more potent than PB in both dog and rat (LTG ED50 values = 4.5 and 11.7 mg.kg-1 i.v. in dogs and rats, respectively). PHT was ineffective in the rat at sublethal doses (less than 40 mg.kg-1 i.v.). In limited studies in marmosets, i.v. administration of both LTG and PHT (both 5-15 mg.kg-1) reduced or abolished afterdischarge. Thus, LTG was a potent anticonvulsant in rat, dog, and marmoset in afterdischarge models of partial (focal) seizures and may be of utility in the treatment of partial seizures in humans.
研究了新型强效抗惊厥药拉莫三嗪（LTG）静脉推注后对氟烷麻醉的狗和狨猴（用于毒性研究的物种）脑电图电诱发后放电持续时间的影响。为作比较，还研究了LTG对氟烷麻醉大鼠海马后放电持续时间的影响，在该物种中已对LTG的抗惊厥作用进行了广泛研究。将已知的抗惊厥药苯妥英（PHT）和苯巴比妥（PB）纳入作比较。LTG在大鼠和狗中均以剂量依赖性方式缩短后放电持续时间；在狗中其效力约为PHT的两倍，在狗和大鼠中均比PB强三至四倍（狗和大鼠的LTG ED50值分别为静脉注射4.5和11.7 mg.kg-1）。在大鼠中，亚致死剂量（静脉注射小于40 mg.kg-1）的PHT无效。在对狨猴的有限研究中，静脉注射LTG和PHT（均为5 - 15 mg.kg-1）均可缩短或消除后放电。因此，在部分（局灶性）癫痫的后放电模型中，LTG在大鼠、狗和狨猴中均为强效抗惊厥药，可能对治疗人类部分性癫痫有用。
