Understanding muscle relaxants by their molecular structure and conformation

Abstract

T HERE ARE more muscle relaxants in use than many other categories of drugs in anesthesia, and muscle relaxants remain a mainstay of anesthesia practice today. Each relaxant was introduced with specific advantages. Maximal benefit to the patient depends on thorough understanding of what they are, how they act and break down, and what their breakdown products do. Examination of their structure and conformation will go a long way toward understanding their action, side effects, metabolism and disposition, and what their metabolites do. Traditionally, we understand the muscle relaxants by their chemical structure and structure-activity relationship (SAR). Such information has helped the development of new and better compounds over the decades, such as pancuronium in the 1970s; atracurium and vecuronium in the 1980s; and mivacurium, cisatracurium, rocuronium, and rapacuronium more recently. Lee I has recently reviewed the SAR of the neuromuscular blocking (NMB) agents and expanded the study into the conformation-activity relationship (CAR). Similar conformational study into other categories of anesthesia-related drugs, such as local anesthetics and narcotics, may also prove useful. Molecular shape is fundamental to organic chemistry and key to drug-receptor interaction. The key-and-lock concept of drug-receptor interaction should be viewed as hand in glove, stressing chirality and molecular conformation. Although structural formula is 2-dimensional, conformation