Czuczwar S J, Gasior M, Kamiński R, Kleinrok Z, Kozicka M, Ossowska G, Pietrasiewicz T
Department of Pharmacology and Toxicology, Lublin Medical University School, Jaczewskiego, Poland.
Mol Chem Neuropathol. 1998 Apr;33(3):149-62. doi: 10.1007/BF02815178.
Excitatory amino acids participate in the generation of seizure activity. Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-mediated events, on the protective activity of conventional antiepileptic drugs against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.p.) did not affect the clonic phase of pentetrazol (injected s.c. at its CD97 of 90 mg/kg) convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was enhanced by GYKI 52466 (10 mg/kg)--the percentage of mice protected was significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg) with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in the chimney test. However, this combination resulted in significant memory deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10 mg/kg) affect either total or free plasma levels of antiepileptic drugs (as measured by immunofluorescence), so a pharmacokinetic interaction is not probable. Finally, the interaction of the non-NMDA receptor antagonist with antiepileptic drugs does not seem promising in the pentetrazol test, recognized as a model of human myoclonic epilepsy.
兴奋性氨基酸参与癫痫发作活动的产生。因此，研究了谷氨酸介导事件的拮抗剂GYKI 52466 [1-(4-氨基苯基)-4-甲氧基-7,8-亚甲基二氧基-5H-2,3-苯并二氮杂䓬盐酸盐]对传统抗癫痫药物对戊四氮的保护活性的影响。GYKI 52466（腹腔注射，剂量高达10 mg/kg）不影响戊四氮（皮下注射，剂量为其90 mg/kg的CD97）惊厥的阵挛期。只有丙戊酸盐（100 mg/kg）的抗戊四氮活性被GYKI 52466（10 mg/kg）增强——受保护小鼠的百分比从20%显著增加到90%。氯硝西泮（0.01）、乙琥胺（50）和苯巴比妥（2.5 mg/kg）的抗惊厥活性未被GYKI 52466（高达10 mg/kg）改变。丙戊酸盐（100 mg/kg）与GYKI 52466（10 mg/kg）的组合不影响在烟囱试验中评估的小鼠表现。然而，这种组合导致在被动回避任务中测量的显著记忆缺陷。在任何情况下，GYKI 52466（10 mg/kg）都不影响抗癫痫药物的总血浆水平或游离血浆水平（通过免疫荧光测量），因此不太可能存在药代动力学相互作用。最后，在被认为是人类肌阵挛癫痫模型的戊四氮试验中，非NMDA受体拮抗剂与抗癫痫药物的相互作用似乎没有前景。
