Opioid analgesics are currently known as the best analgesics.However,toxicity and side effects such as constipation,tolerance and addiction severely limit their clinical application.With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology,researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics,which are different from the traditional morphine skeleton structure modifications.This article focuses on three new research strategies of G-protein biased activation,"one drug-multiple targets"and peripheral activation.The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced,and the latest research progress of representative drugs is briefly reviewed.Among them,the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists,Cebranopadol is a typical"one drug-multiple targets"analgesic,and NFEPP is a representative drug of peripheral opioid receptor agonists.The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.
opioid analgesicbiased agonistone drug-multiple targetsperipheral agonistnew drug development
国家科技期刊平台
NSTL
万方数据
