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0026-895X/97/061077-07$3.00/0
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
All rights of reproduction in any form reserved.
MOLECULAR PHARMACOLOGY 51:1077-1083 (1997).

Carbamazepine Inhibition of Neuronal Na+ Currents: Quantitative Distinction from Phenytoin and Possible Therapeutic Implications

Chung-Chin Kuo, Ren-Shiang Chen, Lu Lu, and Rong-Chi Chen

Department of Physiology, National Taiwan University College of Medicine (C.-C.K., R.-S. C., R.-C.C.), Departments of Neurology (C.-C.K., R.-C.C.) and Rehabilitation (L.L.), National Taiwan University Hospital, and Department of Neurology (R.-C.C.), En-Chu-Kong Hospital, Taipei, 100, Taiwan, Republic of China

Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more effective than the other. This may occur even when optimal therapeutic concentrations are reached with both medications in plasma or the cerebrospinal fluid. In this study, we show that the action of the two drugs on Na+ channels are quantitatively very different. The affinity between inactivated Na+ channels and carbamazepine (apparent dissociation constant ~25 µM) is ~3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is ~38,000 M-1/sec-1, or ~5 times faster than that of phenytoin. It is speculated that carbamazepine may be more effective than phenytoin in treating seizures whose ictal depolarization shift is relatively short, whereas a better response to phenytoin may imply abnormal discharges characterized by more prolonged depolarization.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


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