Effects of anesthetic and anticonvulsant drugs on calcium-dependent efflux of potassium from human erythrocytes.

Anesthetic (halothane, enflurane, isoflurane, chloroform, diethyl ether, pentobarbital, phenyclidine) and anticonvulsant (ethosuximide, phenytoin, phenobarbital, sodium valproate, carbamazepine, delta 9-tetrahydrocannabinol) drugs were investigated for their effects on the calcium-dependent efflux of 86Rb (used as a marker for potassium) from resealed human red blood cells. Most anesthetic agents produced biphasic effects, having stimulatory actions at low (anesthetic) concentrations and inhibitory actions at higher (toxic) concentrations. The drug concentrations required to increase calcium-dependent 86Rb efflux were closely correlated with plasma concentrations required for anesthesia in vivo. Two anticonvulsant agents (phenytoin and phenobarbital) inhibited the efflux process in a concentration-dependent manner, while all other tested anticonvulsants were without significant effects. Neither the anesthetic nor the anticonvulsant substances significantly altered the calcium-independent release of 86Rb. The possibility that general anesthetic and anticonvulsant drugs act on calcium-dependent potassium conductance in the central nervous system, and the therapeutic importance of such actions, is discussed.