TY - JOUR T1 - Carbamazepine Inhibition of Neuronal Na<sup>+</sup> Currents: Quantitative Distinction from Phenytoin and Possible Therapeutic Implications JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1077 LP - 1083 DO - 10.1124/mol.51.6.1077 VL - 51 IS - 6 AU - Chung-Chin Kuo AU - Ren-Shiang Chen AU - Lu Lu AU - Rong-Chi Chen Y1 - 1997/06/01 UR - http://molpharm.aspetjournals.org/content/51/6/1077.abstract N2 - 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 ∼38,000m − 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. ER -