摘要：gabaa受体是中枢神经系统内重要的抑制性受体,有广泛的神经生理活性.由于镇静/抗惊厥药物在临床上的广泛应用,使得其中苯并二氮杂作用位点尤为重要.我们用比较分子场法(CoMFA)对一系列咪唑苯并二氮杂类化合物(BZ)与五种重组受体亚型的亲和力进行了结构活性关系研究,得到的一组模型都有较高的交叉验证系数.并在此基础上,建立了非交叉验证的一组PLS模型.用该组模型对随机选择的6个化合物组成的测试集进行了预测,都得到了相当满意的结果,表明所建立的一组模型具有良好的预测能力.本研究对于设计高亲和力的BZ受体的配基和研究gabaa受体的模型有指导意义.

摘要：General anesthetics constitute some of the most important and widely-used therapeutic drugs in the pharmacotherapeutic armamentarium. They are routinely used effectively and with adequate precaution-safety throughout the world for a multitude of clinical applications, predominantly as adjunctive agents for surgical procedures. Nevertheless, they have potential adverse effects (such as a drop in blood pressure and the inhibition of steroid production), particularly in vulnerable populations such as the very young and the frail elderly. It would be desirable therefore to have alternative agents that are just as efficacious, but have a better safety profile in a broader spectrum of patients. Toward this end, an anesthetic based on a unique chemical core (viz., an N-arylpyrrole derivative) has been reported in preclinical models to produce anesthetic effects without hemodynamic suppression. This lead could pave the way for new general anesthetics that are safer and easier to use.