Velísek L, Velísková J, Ptachewich Y, Shinnar S, Moshé S L
Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461.
Epilepsia. 1995 Feb;36(2):179-85. doi: 10.1111/j.1528-1157.1995.tb00978.x.
We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.
我们测定了N-甲基-D-天冬氨酸（NMDA）受体阻滞剂MK-801（腹腔注射，剂量分别为0.05、0.1和0.5毫克/千克）和苯妥英（PHT，腹腔注射，剂量分别为5、10和20毫克/千克）对9日龄、15日龄、30日龄和60日龄雄性大鼠氟烷诱发的阵挛性和强直-阵挛性癫痫发作的影响。两种药物都有癫痫发作、年龄和剂量特异性效应。MK-801的最高剂量仅对9日龄和60日龄大鼠的氟烷诱发的阵挛性癫痫发作有抗惊厥作用，但对所有年龄段的强直-阵挛性癫痫发作均有抑制作用。MK-801的最低剂量（0.05毫克/千克）仅对15日龄大鼠产生显著的抗惊厥作用。PHT在整个发育过程中对阵挛性癫痫发作均无影响。PHT的两种剂量（10和20毫克/千克）对成年大鼠的强直-阵挛性癫痫发作有抗惊厥作用，但对其他任何年龄组均无此作用。结果表明，NMDA受体在整个发育过程中（尤其是在15日龄大鼠中）对氟烷诱发的强直-阵挛性癫痫发作起重要作用，且PHT的抗惊厥作用在脑发育的不同阶段可能有所不同。
