Conformation, action, and mechanism of action of neuromuscular blocking muscle relaxants.
Since curare was introduced into clinical anaesthesia in 1942, efforts to create better neuromuscular blocking (NMB) muscle relaxants have continued. Today, muscle relaxation remains a mainstay of modern anaesthesia and intensive care. Through manipulation of the traditional structure-action relationships, many new and improved muscle relaxants have been created, and several have been brought to clinical use. However, structure-action relationship is inconsistent and has its limits. Using computer-aided molecular conformational analyses, the conformation-action relationships of NMB agents of various chemical classes have been explored. Conformation, no less than structure, of the NMB agents has shed new light on their mechanisms of action. By reflection, the conformations also suggest new details of the topology of the receptive sites of the nicotinic acetylcholine receptor modeled for the motor endplate of the skeletal muscle.
Department of Anesthesiology, Harbor-UCLA Medical Center Campus of UCLA School of Medicine, 1000 West Carson Street, Torrance, CA 90274, USA. chinglee@ucla.edu
Chingmuh
C
Lee
D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000502:physiology; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D009465:Neuromuscular Agents; D011978:Receptors, Nicotinic