Waser P G, Ganz A J, Pfirrmann R W
Arzneimittelforschung. 1978;28(6):952-6. doi: 10.1002/chin.197841192.
A series of derivatives of 1-(p-sulfamoyl-phenyl)-pyrrolidin-2-one were tested for anticonvulsant properties in rats and mice. The substance 1-(o-chloro-p-sulfamoyl-phenyl)-4-phenyl-pyrrolidin-2-one (1725) was found to have potent anticonvulsant activities in rats and mice against seizures induced by electroshock or pentylenetetrazol. The unsubstituted phenyl ring has to be in position 4, otherwise the activity of the product is weakened. The ortho position of the halogen atom on the N-phenyl is also important for the anticonvulsant effect; chlorine acts better than fluorine. The anticonvulsants tested also potentiate the sleeping time induced by pentobarbitone and attenuate the motor activity of mice. 1-(o-Chloro-p-sulfamoyl-phenyl)-4-phenyl-pyrrolidin-2-one (1725) has a LD50 of 1000 mg/kg p.o.; the lesser active substances generally have a LD50 greater than 5000 mg/kg p.o. Toxic effects of large doses were manifested by sedation and diarrhoea.
对一系列1-(对磺酰胺基苯基)-吡咯烷-2-酮衍生物进行了大鼠和小鼠抗惊厥特性测试。发现物质1-(邻氯-对磺酰胺基苯基)-4-苯基-吡咯烷-2-酮（1725）在大鼠和小鼠中对电休克或戊四氮诱导的惊厥具有强效抗惊厥活性。未取代的苯环必须位于4位，否则产物的活性会减弱。N-苯基上卤素原子的邻位对抗惊厥作用也很重要；氯的效果比氟好。所测试的抗惊厥药还能延长戊巴比妥诱导的睡眠时间，并减弱小鼠的运动活性。1-(邻氯-对磺酰胺基苯基)-4-苯基-吡咯烷-2-酮（1725）经口服的半数致死量为1000 mg/kg；活性较低的物质经口服的半数致死量通常大于5000 mg/kg。大剂量的毒性作用表现为镇静和腹泻。
