Tutka P, Turski W A, Kleinrok Z, Czuczwar S J
Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland.
J Neural Transm (Vienna). 1996;103(3):307-14. doi: 10.1007/BF01271242.
Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene-a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED50 values of aminophylline were 55.7 and 98.4 mg/kg i.p. However, aminophylline (up to 100 mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl- enedioxy-5H-2,3-benzodiazepine (GYKI 52466-a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock-the ED50 values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28 mg/kg s.c., respectively. An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.
氨茶碱可逆转 D-3-(2-羧基哌嗪-4-基)-1-丙烯基-1-膦酸（D-CPP-ene，一种竞争性 N-甲基-D-天冬氨酸拮抗剂）和丙戊酸盐（用作传统抗癫痫药物以作比较）对最大电休克诱发癫痫发作的保护作用。氨茶碱的相应半数有效剂量（ED50）分别为腹腔注射 55.7 和 98.4 毫克/千克。然而，氨茶碱（腹腔注射剂量高达 100 毫克/千克）并不影响 1-(4-氨基苯基)-4-甲基-7,8-亚甲二氧基-5H-2,3-苯并二氮杂卓（GYKI 52466，一种非 N-甲基-D-天冬氨酸拮抗剂）的保护效果。士的宁会影响 D-CPP-ene、GYKI 52466 和丙戊酸盐对最大电休克的保护作用——士的宁逆转 D-CPP-ene、GYKI 52466 或丙戊酸盐抗惊厥作用的半数有效剂量分别为皮下注射 0.082、0.35 和 0.28 毫克/千克。可以推测，士的宁敏感的甘氨酸能受体介导的事件参与了兴奋性氨基酸拮抗剂和丙戊酸盐的抗惊厥活性机制。氨茶碱无法降低 GYKI 52466 的抗惊厥作用，这可能区分出一类新型抗癫痫药物，这类药物在因肺部原因需要使用氨茶碱的癫痫患者中，相较于传统抗癫痫药物具有优势。
