THE ANTICONVULSANT ACTION OF CARBON DIOXIDE: INTERACTION WITH RESERPINE AND INHIBITORS OF CARBONIC ANHYDRASE

¹ Department of Ex?perimental Pharmacology, Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

The anticonvulsant actions of CO2 and inhibitors of carbonic anhydrase show the following similarities : 1) they are antagonized by reserpine in both rats and mice ; 2) action is restored by the administration of dl- dopa to reserpine- treated mice, indicating involvement of catecholamines ; and 3) in rats, the antagonistic action of reserpine is surmountable by both agents. The two agents differ in their anticonvulsant effect in mice ; antagonism by reserpine is insurmountable by carbonic anhydrase inhibi tore, but is surmountable by CO2 . Treatment with methazolamide followed by CO2 pro duces a greater anticonvulsant effect in mice and possibly also in rats than would be expected on the basis of a similar joint action. This phenomenon most probably is due to the enhancement of the anticonvulsant effect of methazolamide by the acidosis produced by equilibration with CO2 . Reserpine antagonism of the anticonvulsant action of CO2 does not appear to be mediated either by changes in brain excitability or via action on the blood CO2 buffer system. The results support the belief that the anticonvulsant action of carbonic anhydrase inhibitors is mediated by disequilibrium of the CO2 buffer system.