[Development of new antiepileptics. IV. Anticonvulsant activity of some derivatives of 1-(p-sulfamoyl-phenyl)-pyrrolidin-2-one (author's transl)].
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.
D000818:Animals; D000927:Anticonvulsants; D004597:Electroshock; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011760:Pyrrolidinones; D010424:Pentobarbital; D010433:Pentylenetetrazole
Die Entwicklung neuer Antiepileptika. IV. Antikonvulsive Wirkung einiger 1-(p-Sulfamoyl-phenyl)-pyrrolidin-2-on-Derivate).