Carbamazepine inhibition of neuronal Na+ currents: Quantitative distinction from phenytoin and possible therapeutic implications

被引:136
作者
Kuo, CC
Chen, RS
Lu, L
Chen, RC
机构
[1] NATL TAIWAN UNIV HOSP,DEPT NEUROL,TAIPEI 100,TAIWAN
[2] NATL TAIWAN UNIV HOSP,DEPT REHABIL,TAIPEI 100,TAIWAN
[3] EN CHU KONG HOSP,DEPT NEUROL,TAIPEI 100,TAIWAN
关键词
D O I
10.1124/mol.51.6.1077
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 similar to 25 mu M) is similar to 3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is similar to 38,000 M-1/sec(-1), or similar to 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.
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收藏
页码:1077 / 1083
页数:7
相关论文
共 23 条
[1]   FREQUENCY-DEPENDENT ACTION OF PHENYTOIN ON LAMPREY SPINAL AXONS [J].
ADLER, EM ;
YAARI, Y ;
DAVID, G ;
SELZER, ME .
BRAIN RESEARCH, 1986, 362 (02) :271-280
[2]   LIDOCAINE BLOCK OF CARDIAC SODIUM-CHANNELS [J].
BEAN, BP ;
COHEN, CJ ;
TSIEN, RW .
JOURNAL OF GENERAL PHYSIOLOGY, 1983, 81 (05) :613-642
[3]  
BEAN BP, 1984, P NATL ACAD SCI USA, V81, P6386
[4]  
Bourgeois Blaise F. D., 1993, P726
[5]   MOLECULAR MECHANISMS OF LOCAL-ANESTHESIA - A REVIEW [J].
BUTTERWORTH, JF ;
STRICHARTZ, GR .
ANESTHESIOLOGY, 1990, 72 (04) :711-734
[6]   CELLULAR MECHANISMS OF EPILEPSY - A STATUS-REPORT [J].
DICHTER, MA ;
AYALA, GF .
SCIENCE, 1987, 237 (4811) :157-164
[8]  
HILLE B, 1993, IONIC CHANNELS EXCIT, P408
[9]   CONCENTRATION OF CARBAMAZEPINE (TEGRETOL) IN SERUM AND IN CEREBROSPINAL-FLUID IN PATIENTS WITH EPILEPSY [J].
JOHANNES.SI ;
STRANDJO.RE .
EPILEPSIA, 1973, 14 (04) :373-379
[10]   NA+ CHANNELS MUST DEACTIVATE TO RECOVER FROM INACTIVATION [J].
KUO, CC ;
BEAN, BP .
NEURON, 1994, 12 (04) :819-829