3-Sulfamoylmethyl-1,2-benzisoxazole, a new type of anticonvulsant drug. Pharmacological profile.

Abstract

The anticonvulsant and neurotoxic properties of 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810) have been demonstrated. AD-810 suppressed electrically and chemically induced maximal seizures but did not prevent minimal seizures in experimental animals. In rats, rabbits and dogs, the anticonvulsant activity of AD-810 against maximal electroshock seizures was more potent than those of diphenylhydantoin and carbamazepine. In rats, AD-810 showed more rapid onset as well as longer duration of anticonvulsant activity than the above two drugs. The anticonvulsant effect of AD-810 was reduced but not abolished by reserpine. No tolerance developed to the anticonvulsant action of AD-810 by consecutive treatment. The compound showed much less neurotoxicity and lethal toxicity than the existing antiepileptic drugs for grand mal, and also showed the least hypnotic effect by itself or by combination with hexobarbital. Thus, AD-810 possesses a profile of anticonvulsant activity most similar to that of diphenylhydantoin or carbamazepine, providing a high protective index as well as other favorable properties.