Hashimoto Yasuhiko, Araki Hiroaki, Gomita Yutaka
Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
Pharmacol Biochem Behav. 2003 Mar;74(4):909-15. doi: 10.1016/s0091-3057(03)00013-3.
The effects of acute and repeated administration of MK-801 on flurothyl (FE)-induced seizure were investigated in mice. In the acute effect of MK-801 (0.01-0.1 mg/kg ip) in naive and FE-kindled mice, there were no changes on the latencies of clonic seizures. However, MK-801 dose-dependently inhibited both latencies and incidence of tonic seizures in mice and suppressed the grade of seizure severity in FE-kindled mice. Repeated administration of MK-801 at doses of 0.01 and 0.1 mg/kg 2 h prior to each exposure to FE for 8 days did not show any effects on the latencies of clonic seizure. However, seizure severity was significantly exacerbated in the 0.1 mg/kg treated group when mice were re-exposed to FE without MK-801 1 week after the last administration. A week after the repeated administration of MK-801 at a dose of 0.1 mg/kg for 8 days without exposure to FE, mice were exposed to FE 2 h after readministration of MK-801 until tonic seizure occurred. The latencies of clonic seizures were almost the same in the acute experiment in naive controls. The latency of tonic seizure was significantly delayed compared to the acute experiment with MK-801 at a dose of 0.1 mg/kg. These findings suggested that MK-801 possessed an anticonvulsant action against FE-induced tonic seizure. However, the efficacy of this acute effect of MK-801 was impaired at 1 week of withdrawal after repeated administrations. This may be related in part to the changes in sensitivity to NMDA receptors.
研究了急性和重复给予MK - 801对氟替尔（FE）诱导的小鼠癫痫发作的影响。在对未致敏和FE点燃小鼠急性给予MK - 801（0.01 - 0.1 mg/kg腹腔注射）时，阵挛性癫痫发作的潜伏期没有变化。然而，MK - 801剂量依赖性地抑制小鼠强直性癫痫发作的潜伏期和发生率，并抑制FE点燃小鼠的癫痫严重程度分级。在每次暴露于FE前2小时重复给予0.01和0.1 mg/kg剂量的MK - 801，持续8天，对阵挛性癫痫发作的潜伏期没有任何影响。然而，在最后一次给药1周后，当小鼠在没有MK - 801的情况下再次暴露于FE时，0.1 mg/kg治疗组的癫痫严重程度显著加重。在不暴露于FE的情况下，以0.1 mg/kg剂量重复给予MK - 801 8天，1周后，在再次给予MK - 801 2小时后将小鼠暴露于FE，直到强直性癫痫发作。在未致敏对照的急性实验中，阵挛性癫痫发作的潜伏期几乎相同。与以0.1 mg/kg剂量的MK - 801进行的急性实验相比，强直性癫痫发作的潜伏期显著延迟。这些发现表明，MK - 801对FE诱导的强直性癫痫发作具有抗惊厥作用。然而，在重复给药后停药1周时，MK - 801这种急性效应的疗效受损。这可能部分与对NMDA受体的敏感性变化有关。
