Apland J P, Cann F J
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Brain Res Bull. 1995;37(3):311-6. doi: 10.1016/0361-9230(95)00038-g.
The anticonvulsant properties of memantine (Mem) were compared to those of MK-801. Extracellular field recordings were obtained from area CA1 of guinea pig hippocampal slices in a total submersion chamber at 32 degrees C in normal oxygenated artificial cerebrospinal fluid (ACSF). Evoked responses were elicited by 0.07 Hz stimulation of the Schaffer collateral and commissural fibers. Bath perfusion of slices with Mg(2+)-free ACSF and N-methyl-D-aspartate (NMDA)-containing ACSF induced epileptiform afterdischarges following evoked responses. Pretreatment of slices by bath application of 100 microM Mem for 18-20 min prevented epileptiform afterdischarges under both convulsant conditions. Perfusion with 100 microM Mem alone for up to 50 min had no discernible effect on evoked responses. MK-801 was as effective at < or = 10 microM and required application for over 15 min to suppress afterdischarges completely. Both Mem and MK-801 suppressed epileptiform activity when applied after such activity was induced by NMDA or MG(2+)-free ACSF. The EC50 of Mem was 16.6 microM and that of MK-801 was 0.19 microM for blocking NMDA-induced evoked response suppression. Thus, in the guinea pig hippocampal slice preparation, Mem appeared to have anticonvulsant properties qualitatively similar to those of MK-801, but was 10-100 fold less potent.
将美金刚（Mem）的抗惊厥特性与MK-801的抗惊厥特性进行了比较。在32摄氏度的正常含氧人工脑脊液（ACSF）中，于全浸没式实验箱中从豚鼠海马切片的CA1区获取细胞外场记录。通过以0.07赫兹刺激海马联合纤维和绍菲侧支纤维来诱发反应。用不含镁的ACSF和含N-甲基-D-天冬氨酸（NMDA）的ACSF对切片进行灌流，会在诱发反应后引发癫痫样放电。通过在浴槽中应用100微摩尔的美金刚预处理切片18 - 20分钟，可在两种惊厥条件下预防癫痫样放电。单独用100微摩尔的美金刚灌流长达50分钟，对诱发反应没有明显影响。MK-801在浓度小于或等于10微摩尔时同样有效，并且需要应用超过15分钟才能完全抑制放电。当在由NMDA或不含镁的ACSF诱导出这种活动后应用美金刚和MK-801时，二者均可抑制癫痫样活动。在阻断NMDA诱导的诱发反应抑制方面，美金刚的半数有效浓度（EC50）为16.6微摩尔，MK-801的EC50为0.19微摩尔。因此，在豚鼠海马切片制备中，美金刚似乎具有与MK-801在性质上相似的抗惊厥特性，但效力要低10 - 100倍。
