ANTICONVULSANT ACTIVITY OF SOME CARBINYLUREAS

¹ Chemical Therapeutics Research and Medical Sciences Research Laboratories, Miles Laboratories, Inc.' Elkhart, Indiana

Three carbinylureas, MA-321 (1-methylcyclohexylurea), MA-337 (1-methylcyclopentylurea) and MA-367 (1-ethylcyclopentylurea) given orally have been found to have anticonvulsant properties in rats and dogs. They are comparable in potency to such anticonvulsants as trimethadione and diphenylhydantoin. All three also have sedative-hypnotic, antiemetic, but little or no hypotensive effects.

MA-337 and MA-367 afford protection against both electroconvulsions and chemoconvulsions, resembling carbromal and phenobarbital in these respects. MA-337 is effective at a lower antielectroconvulsant dose than diphenylhydantoin, on both single and daily dosage, while MA-367 is effective at a lower antichemoconvulsant dose than trimethadione on single but not on daily dosage. The antielectroconvulsant effect of MA-367 improves on daily dosage, equalizing that of MA-337. No tolerance or cumulation to the lethal effects of either MA-337 or MA-367 occurs on daily dosage.

MA-321 is an antichemoconvulsant like trimethadione, which offers no protection against electroconvulsions. It has about the same activity as MA-367 and trimethadione, and its antichemoconvulsant effectiveness undergoes less change on daily dosage than that of MA-367. It does not induce tolerance or cumulation to lethal effects.

All three compounds, given orally at 15 and 22% of the A-LD50 daily for 6 months, produce no abnormality of the cellular elements of the blood, or any pathological change in the liver, spleen, kidney or alimentary tract.