碩士 / 國立臺灣大學 / 生理學研究所 / 84 / Abstract Use-dependent block of sodium channels has
been demonstrated to underlie the action of various
antiepileptic, antiarrhythmic, and local anesthetic agents.
Recent studies on mammalian central neurons revealed that
anticonvulsant phenytoin binds selectively to the
inactivated states of sodium channels. Moreover, the voltage-
dependent binding kinetics and affinity of a certain
anticonvulsant may play a key role in understanding the
clinical effect of the drug. For comparison, we studied
the action of carbamazepine (a very common antiepileptic
drug) and lidocaine (an occasionally used drug for
treating status epilepticus) in rat hippocampal neurons.
Whole-cell patch-clamp technique was used to investigate the
on and off rates of sodium channel block by carbamazepine and
lidocaine at various membrane potentials. The on rates of
carbamazepine and lidocaine were linearly related to drug
concentrations and with rate constant of 40000 per M per
second and 30000 per M per second, respectively. The off
rates were not dependent on drug concentration. The
binding affinities defined by assuming one to one binding
between drug and channel molecules increased
with membrane depolarization, and the estimated Kd's of
binding to inactivated sodium channels were 28 μ M
(Carbamazepine) and 17 μ M (Lidocaine). The lower
affinity but higher binding rate constant of carbamazepine may
explain the differences in clinical efficacy from phenytoin to
certain seizure types. Also, to clarify the binding
characteristics of these drugs may improve our
understanding of the possible discharge patterns of the
epileptic neurons.
| Identifer | oai:union.ndltd.org:TW/084NTU00116002 |
| Date | January 1996 |
| Creators | Chen, Ren-Shiang, 陳仁祥 |
| Contributors | Kuo, Chung-Chin, 郭鐘金 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 75 |
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