Kenakin Terry
Department of Pharmacology, University of North Carolina School of Medicine , Chapel Hill, North Carolina 27516, United States.
ACS Chem Neurosci. 2016 Nov 16;7(11):1472-1473. doi: 10.1021/acschemneuro.6b00330. Epub 2016 Oct 14.
The modification of ongoing chemical signaling in the brain through allosteric modification of seven transmembrane receptors offers a wealth of diverse beneficial outcomes in drug therapy. Specifically, biased agonism can emphasize beneficial signals and de-emphasize harmful signals thus increasing the effectiveness of agonists and opening up new vistas for previously precluded drug targets. In addition, the modification of natural agonism through positive and negative allostery can provide useful rejuvenation of failing systems.
通过对七跨膜受体进行变构修饰来改变大脑中正在进行的化学信号传导，在药物治疗中可带来诸多不同的有益结果。具体而言，偏向性激动作用可强化有益信号并弱化有害信号，从而提高激动剂的有效性，并为之前无法涉及的药物靶点开辟新前景。此外，通过正变构和负变构对天然激动作用进行修饰，可为功能衰退的系统提供有益的恢复作用。
