Waser P G, Ganz A J, Pfirrmann R W
Arzneimittelforschung. 1977;27(10):1942-53.
A series of newly synthesized N-phenyl-substituted derivatives of succinimide were screened for anticonvulsant activity. Addition of a sulfonamide group in the p-position was of great consequence for the anticonvulsant effect. Substitution of a halogen in the m- or o-position improved activity against electroshock induced seizures. Pentylenetetrazole convulsions could only be prevented by few of these substances in smaller than 200 mg/kg oral doses. Activity could be further enhanced by adding more aliphatic or aromatic groups to the succinimide ring. The lethal doses of most of the active succinimides were higher than 5000 mg/kg p.o. With sublethal doses mice sometimes become drowsy and had myoclonic seizures and/or diarrhoea. At therapeutic dose levels kinetic disturbances, potentiation of pentobarbitone hypnosis or analgesia were rarely observed.
对一系列新合成的琥珀酰亚胺 N-苯基取代衍生物进行了抗惊厥活性筛选。在对位添加磺酰胺基团对抗惊厥作用有重大影响。在间位或邻位取代卤素可提高对电休克诱发惊厥的活性。只有少数这些物质在口服剂量小于 200 mg/kg 时能预防戊四氮惊厥。通过向琥珀酰亚胺环添加更多脂肪族或芳香族基团,活性可进一步增强。大多数活性琥珀酰亚胺的致死剂量高于 5000 mg/kg 口服。用亚致死剂量时,小鼠有时会变得嗜睡,并出现肌阵挛性惊厥和/或腹泻。在治疗剂量水平,很少观察到动力学紊乱、戊巴比妥催眠或镇痛作用增强。