Effects of intravenous sedatives on higher brain function and basic research of development of new intravenous sedatives

仅具有苯二氮卓类药物的抗焦虑或镇静作用的非苯二氮卓类药物的开发始于20世纪80年代后半期。这些药物的开发采用两种方法：开发部分苯二氮卓受体激动剂，以及开发对苯二氮卓受体结合位点存在的GABAA受体a亚基具有选择性的药物。焦虑选择性药物是使用前一种方法开发的，而镇静选择性药物是由后一种方法产生的。采用双探针微透析法研究了焦虑选择性药物Y-23684和镇静选择性药物唑吡坦对中枢神经系统的作用。该方法表明，焦虑选择性药物抑制应激状态下蓝斑-内侧前额叶皮层去甲肾上腺素神经活动的增强，而镇静选择性药物抑制应激状态下腹侧被盖区-伏隔核多巴胺神经元活动的增强。这些发现表明，对神经网络影响的差异与抗焦虑或镇静作用的选择性有关。

The development of non-benzodiazepine drugs that have only the anxiolytic or sedative action of benzodiazepines started in the latter half of the 1980's. These drugs have been developed using two approaches: development of partial benzodiazepine receptor agonists, and development of drugs with selectivity for the a subunit of the GABAA receptor, at which the benzodiazepine receptor binding site exists. Anxioselective drugs have been developed using the former approach, whereas sedative-selective drugs have emerged from the latter.The actions of the anxioselective drug Y-23684 and the sedative-selective drug zolpidem on the central nervous system have been studied by dual-probe microdialysis. This approach has shown that anxioselective drugs suppress accentuation of the locus coeruleus-medial prefrontal cortex norepinephrine neural activity under stress, while sedative-selective drugs suppress accentuation of the ventral tegmental area-nucleus accumbens dopamine neuron activity in the stress state. These findings suggest that the difference in the effect on the neural network relates to the selectivity for anxiolytic or sedative action.