title: Monod-Wyman-Changeux allosteric mechanisms of action and the pharmacology of etomidate.
abstract: OBJECTIVE
  Formal Monod-Wyman-Changeux allosteric mechanisms have proven valuable in framing research on the mechanism of etomidate action on its major molecular targets, γ-aminobutyric acid type A (GABAA) receptors. However, the mathematical formalism of these mechanisms makes them difficult to comprehend.
  
  
  RESULTS
  We illustrate how allosteric models represent shifting equilibria between various functional receptor states (closed versus open) and how co-agonism can be readily understood as simply addition of gating energy associated with occupation of distinct agonist sites. We use these models to illustrate how the functional effects of a point mutation, α1M236W, in GABAA receptors can be translated into an allosteric model phenotype.
  
  
  CONCLUSIONS
  Allosteric co-agonism provides a robust framework for design and interpretation of structure-function experiments aimed at understanding where and how etomidate affects its GABAA receptor target molecules.
authors.affiliation: Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. saforman@partners.org
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Forman
mesh_terms: D000494:Allosteric Regulation; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D005045:Etomidate / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D018686:Anesthetics, Intravenous; D018755:GABA Agonists; D011963:Receptors, GABA-A; D005045:Etomidate