CONTINGENT TOLERANCE TO CARBAMAZEPINE - A PERIPHERAL-TYPE BENZODIAZEPINE MECHANISM

被引：30

作者：

WEISS, SRB ^{[1
]}

POST, RM ^{[1
]}

机构：

[1] NIMH, BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1991年 / 193卷 / 02期

关键词：

CONTINGENT TOLERANCE; BENZODIAZEPINE RECEPTORS (PERIPHERAL-TYPE); CARBAMAZEPINE; KINDLING;

D O I：

10.1016/0014-2999(91)90031-K

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Rats were tested for anticonvulsant responsivity to agents active at central and peripheral-type benzodiazepine receptors before and after they were made tolerant to the anticonvulsant effects of carbamazepine on amygdala-kindled seizures. Tolerance to carbamazepine in this paradigm is a contingent process; it occurs when the drug is administered prior to, but not following the kindled seizure. In animals tolerant to carbamazepine, cross-tolerance was observed to the anticonvulsant effects of PK11195, which is active at peripheral-type benzodiazepine receptors, but not to diazepam, which affects central-type benzodiazepine receptors. In animals treated with carbamazepine after the kindled seizure (not tolerant), no alteration in the anticonvulsant effect of PK11195 was observed. These data extend previous biochemical and pharmacological findings suggesting the importance of peripheral-type benzodiazepine receptor mechanisms in the anticonvulsant effects of carbamazepine and suggest a role for this site in the process of contingent tolerance development.

引用

页码：159 / 163

页数：5

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