Muscarinic acetylcholine receptor modulators derived from natural toxins and diverse interaction mod

• 作 者: XU JianRong WANG Hao CHEN HongZhuan
• 机 构: Department of Pharmacology, Institute of Medical Sciences, School of Medicine, Shanghai Jiao Tong Un
• 出 处: Science China(Chemistry)
• 发表日期: 2013年10期
• 关键词: physiological acetylcholine residues elucidation selectivity affinity diverse mu

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 phlegmarine-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 understanding 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.

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. Advances in medicinal chemistry and structural biology, more and more mAChR 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 phlegmarine-like modulators. This review, we focus on various mAChR modulators derived from natural toxins on the basis of the receptor-ligand interaction modes.The understanding of the affinity, the int rinsic efficacy, and the selectivity of mAChRs modulators may lead to the discovery of new drug leads for the treatment of diseases related to mAChRs.