Takazawa A, Anderson P, Abraham W C
Department of Psychology, University of Otago, Dunedin, New Zealand.
Epilepsia. 1990 Sep-Oct;31(5):496-502. doi: 10.1111/j.1528-1157.1990.tb06097.x.
The effects of dextromethorphan (DM), a nonopioid antitussive and a functional N-methyl-D-aspartate (NMDA) antagonist, on expression and development of amygdaloid kindled seizures were examined. The maximum anticonvulsant effect of DM (30 mg/kg) on fully kindled seizures appeared within 30 min of administration and lasted for at least 2 h. DM decreased, in a dose-dependent manner [10-70 mg/kg, intraperitoneally (i.p.)], the severity of kindled seizures 30 min after injection, but the estimated ED50 was 3 times higher than the previously reported value for maximal electroshock convulsions. Furthermore, the high dose (70 mg/kg), while suppressing kindled seizures, produced myoclonus which coincided with EEG spike activity in the amygdala and the cortex. When tested on the development of kindling, 30 mg/kg DM retarded the growth of afterdischarge in the amygdala and the cortex, but had no effect on the development of behavioral seizures. DM 60 mg/kg accelerated development of kindling and produced spontaneous seizures. These results indicate that DM, unlike other NMDA antagonists, has a narrow therapeutic window as an anticonvulsant on kindled seizures and that higher doses may potentiate the kindling process.
研究了右美沙芬（DM），一种非阿片类镇咳药和功能性N-甲基-D-天冬氨酸（NMDA）拮抗剂，对杏仁核点燃性癫痫发作的表达和发展的影响。DM（30mg/kg）对完全点燃性癫痫发作的最大抗惊厥作用在给药后30分钟内出现，并持续至少2小时。DM以剂量依赖性方式[10 - 70mg/kg，腹腔内（i.p.）]降低注射后30分钟点燃性癫痫发作的严重程度，但估计的半数有效剂量（ED50）比先前报道的最大电休克惊厥的值高3倍。此外，高剂量（70mg/kg）在抑制点燃性癫痫发作的同时，产生了肌阵挛，这与杏仁核和皮质中的脑电图尖峰活动一致。当测试对点燃发展的影响时，30mg/kg DM延缓了杏仁核和皮质中放电后电位的增长，但对行为性癫痫发作的发展没有影响。60mg/kg DM加速了点燃的发展并产生了自发性癫痫发作。这些结果表明，与其他NMDA拮抗剂不同，DM作为点燃性癫痫发作的抗惊厥药具有狭窄的治疗窗口，并且更高剂量可能会增强点燃过程。
