Czuczwar S J, Turski W A, Kleinrok Z
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
Metab Brain Dis. 1996 Jun;11(2):143-52. doi: 10.1007/BF02069501.
Excitatory amino acid antagonists possess anticonvulsant properties in many experimental models of epilepsy and were shown to potentiate the protective activity of conventional antiepileptics against maximal electroshock-induced seizures in mice. Combined treatments of valproate with either D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid or dizocilpine (NMDA antagonists), which provided a 50% protection against maximal electroshock, produced no side-effects, as measured in the chimney test (motor coordination) or passive avoidance task (long-term memory). Valproate alone at its ED50 against maximal electroshock, induced severe adverse effects. The NMDA antagonists, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid, memantine, procyclidine, and trihexyphenidyl also potentiated the protective activity of conventional antiepileptics but these treatments were associated with considerable side-effects. The non-NMDA receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline and 1-(amino-phenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine, also enhanced the anticonvulsive action of antiepileptic drugs against maximal electroshock, and these combinations generally resulted in no adverse effects. The potential clinical importance of some combinations of common antiepileptics with excitatory amino acid antagonists is postulated.
兴奋性氨基酸拮抗剂在许多癫痫实验模型中具有抗惊厥特性，并且已表明其能增强传统抗癫痫药物对小鼠最大电休克诱发惊厥的保护活性。丙戊酸盐与D，L-(E)-2-氨基-4-甲基-5-膦酰基-3-戊烯酸或地佐环平（NMDA拮抗剂）联合治疗，可对最大电休克提供50%的保护，且在烟囱试验（运动协调性）或被动回避任务（长期记忆）中未产生副作用。单独使用丙戊酸盐达到其对最大电休克的半数有效剂量时，会诱发严重不良反应。NMDA拮抗剂D-3-(2-羧基哌嗪-4-基)-1-丙烯基-1-膦酸、美金刚、丙环定和苯海索也增强了传统抗癫痫药物的保护活性，但这些治疗会伴随相当多的副作用。非NMDA受体拮抗剂2,3-二羟基-6-硝基-7-氨磺酰基苯并(F)喹喔啉和1-(氨基苯基)-4-甲基-7,8-亚甲基二氧基-5H-2,3-苯并二氮杂卓也增强了抗癫痫药物对最大电休克的抗惊厥作用，并且这些联合用药通常不会产生不良反应。推测了一些常见抗癫痫药物与兴奋性氨基酸拮抗剂联合用药的潜在临床重要性。
