GABA_B受体变构调节剂及其应用研究进展

Research progress of GABA_B receptor allosteric modulators and their applications

GABA_B受体参与调控多种重要生理和病理过程,是重要药物靶点之一。目前,针对该受体的药物开发主要为其正位配体,上市药物非常有限。变构调节剂是GABA_B受体的新型配体,通过作用于GABA_B受体变构调节位点,特异性调控受体活性,具有很好的受体特异性和药理学特性。多种动物模型实验结果显示,GABA_B受体变构调节剂可以协同正位配体,有效改善如药物成瘾、疼痛等多种疾病症状,并具有不同于正位配体的药效特点。GABA_B受体变构调节剂生理效应机制较独特,具有较好的医药应用价值和前景,进一步的临床试验验证和变构调节剂精细作用机制的深入研究,将为新药开发提供新思路。该文介绍了GABA_B受体变构调节剂的最新研究及其应用进展,并对这类化合物的作用优势和应用前景进行概述。

GABA B receptor involves in the regulation of diverse physiological and pathological processes and has been one of the most important drug targets.Currently,drug development for the receptor mainly focuses on orthosteric ligands,and the marketed drugs are very limited.Allosteric modulators are novel ligands of the GABA B receptor,which specifically regulate receptor activity by acting on the allosteric modulatory sites and possess good receptor specificity and pharmacological characteristics.A variety of animal model experiments showed that GABA B receptor allosteric modulators could effectively improve the symptoms of various diseases,such as drug addiction and pain,by cooperating with orthosteric ligands,and exert novel characteristics other than orthosteric ligands.The unique physiological effects of GABA B receptor allosteric modulators set them as promising candidates,showing excellent medical application value and prospects.Further clinical trial verification and investigation of the detailed mechanism of allosteric modulators will provide new ideas for the development of new drugs.