Electrophysiological actions of benzodiazepines.
Electrophysiological actions of benzodiazepines.
复制标题
DOI：
--
复制
发表时间：
1980-10
期刊：
影响因子：
--
通讯作者：
H. M. Geller;B. Hoffer;D. Taylor
中科院分区：
文献类型：
--
作者：
H. M. Geller;B. Hoffer;D. Taylor
电生理研究表明，局部或全身应用苯二氮卓类药物可降低中枢神经系统的兴奋性。本文总结的研究表明，苯二氮卓类药物对兴奋性的抑制是γ -氨基丁酸（GABA）介导的抑制增加的结果。这种抑制的增加可能是由于苯二氮卓类药物增加了一些GABA能神经元的活性，也可能是由于苯二氮卓类药物对一些突触后受体部位的GABA作用的调节作用。苯二氮卓类药物的剂量对神经元兴奋性或膜极化没有任何直接影响，观察到这种调节作用。特异性试验表明苯二氮卓类药物不增强甘氨酸或单胺如去甲肾上腺素或血清素介导的抑制作用。本文还介绍了惊厥苯二氮卓类化合物的实验结果，该化合物可导致GABA介导的抑制特异性降低，并根据苯二氮卓类受体、GABA受体和氯离子载体功能连接的模型对数据进行了讨论。此外，我们还提出，GABA的一些突触后作用可能受到苯二氮卓类受体占据的持续调节，并且苯二氮卓类受体的占据可能对GABA引起的氯离子通透性增加是允许的。
Electrophysiological investigations have revealed that benzodiazepines, applied either locally or systemically, reduce central nervous system excitability. The studies summarized here indicate that this depression of excitability by benzodiazepines is a result of an increase in gamma-aminobutyric acid (GABA) mediated inhibition. This increase in inhibition may result from benzodiazepines increasing the activity of some GABAergic neurons and also from a modulatory action of benzodiazepines on GABA actions at some postsynaptic receptor sites. The modulatory action is observed with doses of benzodiazepines that do not cause any direct effects on neuronal excitability or membrane polarization. Specificity tests indicate that benzodiazepines do not enhance inhibition mediated by glycine or monoamines such as norepinephrine or serotonin. Results of experiments with a convulsant benzodiazepine compound, which causes a specific reduction in GABA-mediated inhibition, are also presented, The data are discussed in terms of a model in which the benzodiazepine receptor, the GABA receptor, and the chloride ionophore are functionally linked. Furthermore, it is proposed that some postsynaptic actions of GABA may be continually regulated by the occupancy of a benzodiazepine receptor, and that occupancy of the benzodiazepine receptor may be permissive for the GABA-elicited increase in chloride ion permeability.