Muscarinic acetylcholine receptors （mAChRs） play crucial roles in various physiological functions and pathophysiological processes. Acetylcholine （ACh）, as a classical ligand and one of the pivotal neurotransmitte...Muscarinic acetylcholine receptors （mAChRs） play crucial roles in various physiological functions and pathophysiological processes. Acetylcholine （ACh）, as a classical ligand and one of the pivotal neurotransmitters, serves as a prototype for the elucidation of molecular interaction and the development of mimicked and antagonized agents. With the advances in medicinal chemistry and structural biology, more and more mAChRs modulators derived from natural toxins have been identified. Based on the chemical structures and the receptor-ligand interaction modes, these mAChRs modulators can be divided into orthosteric modulators, allosteric modulators and other modulators. Moreover, allosteric modulators can be further divided into three groups： alcuronium-like modulators, staurosporine-like modulators, and phlegrnarine-like modulators. In this review, we focus on various mAChRs modulators derived from natural toxins on the basis of the receptor-ligand interaction modes. The under- standing of the affinity, the intrinsic efficacy, and the selectivity of mAChRs modulators may lead to the discovery of new drug leads for the treatment of diseases related to mAChRs.展开更多
基金supported by the National Basic Research Program of China(973 Program,2010CB529806)the International Science&Technology Cooperation Program of China(2011DFA33180)
文摘Muscarinic acetylcholine receptors （mAChRs） play crucial roles in various physiological functions and pathophysiological processes. Acetylcholine （ACh）, as a classical ligand and one of the pivotal neurotransmitters, serves as a prototype for the elucidation of molecular interaction and the development of mimicked and antagonized agents. With the advances in medicinal chemistry and structural biology, more and more mAChRs modulators derived from natural toxins have been identified. Based on the chemical structures and the receptor-ligand interaction modes, these mAChRs modulators can be divided into orthosteric modulators, allosteric modulators and other modulators. Moreover, allosteric modulators can be further divided into three groups： alcuronium-like modulators, staurosporine-like modulators, and phlegrnarine-like modulators. In this review, we focus on various mAChRs modulators derived from natural toxins on the basis of the receptor-ligand interaction modes. The under- standing of the affinity, the intrinsic efficacy, and the selectivity of mAChRs modulators may lead to the discovery of new drug leads for the treatment of diseases related to mAChRs.
