筛选镇静催眠药物的动物实验评价

A review of animal experiments used for sedative-hypnotic drug screening

失眠在现代社会广泛存在,影响近1/3的人口,进一步寻找安全有效的镇静催眠药物是人民健康和市场的共同需求。尽管研究手段众多,但动物实验仍然是发现、验证与评价镇静催眠药物的常用手段,主要包括旷场实验、戊巴比妥钠阈下/阈剂量协同受试药物诱导翻正反射实验、基于诱导失眠模型的验证实验以及脑电图检测等。其中,旷场实验通过观察动物的自主活动初步判断受试药物的镇静效应;戊巴比妥钠协同诱导翻正反射实验所产生的睡眠指标(睡眠潜伏期、睡眠时间)可初步揭示受试药物的催眠作用;某些应激方式或药物能够使动物在一段时间内持续处于失眠状态,可判断受试药物对失眠的防治情况;脑电图是睡眠评价的金指标,可观察受试药物对睡眠结构的调整,进一步筛选能够恢复生理性睡眠的受试药物。笔者对常用的筛选评价手段进行综述,为镇静催眠药物的研究和开发提供参考。

Insomnia is very common in modern society,affecting approximately one third of the general population.Developing safe and effective sedative-hypnotic medication is a basic need for people’s health and an attractive goal for pharmaceutical companies.Although many research methods are available,animal experiments are still used regularly to discover,verify,and evaluate sedative-hypnotic drugs that include open field test,pentobarbital subthreshold/threshold dose-induced righting reflex test,insomnia animal model,and electroencephalogram(EEG).Among these,the open field test is used to evaluate the sedative effect of drugs through observations of autonomic activities.The sleep indexes generated in the pentobarbital-induced righting reflex,such as sleep latency and sleep time,are used to preliminarily reveal the hypnotic effects.Some kinds of stress paradigms or medications could induce insomnia for a period of time,and thus they are used to estimate the effect of drugs on improving insomnia.EEG,which is the gold standard,can reflect the adjustment effect of drugs on sleep structure and further screen the test drug’s ability to restore physiological sleep.Therefore,this paper reviews commonly used screening method to provide references for the research and development of sedative-hypnotic drugs.