Molecular mechanisms of anesthesia.
Anesthesia was a blessing to humankind. It is a miracle that simple molecules such as chloroform (CHCl3), diethyl ether (CH3.CH2.O.CH2.CH3), or nitrous oxide (N2O) induce a state of unconsciousness where patients can tolerate surgery. The diversity of the structures of these molecules indicates that there are no common receptors. The action of anesthetics is nonspecific and physical. After the demonstration by Meyer and Overton that anesthetic potencies correlate to their solubility into olive oil, the nonspecific lipid theories monopolized anesthesia theories for almost a century. The dominance of lipid theories invited repulsions against the nonspecificity idea. Protein theories that stress receptor bindings became the top mode. Nevertheless, the wide varieties of anesthetic molecules and the wide varieties of responding systems are difficult to reconcile with the specific interaction concept. This article discusses the recent progress and controversies on the molecular mechanisms of anesthesia. Anesthetics are unique drugs in pharmacology. They affect all macromolecules. The only comparable drugs are disinfectants. Both are nonspecific drugs. We use alcohols and phenols to wipe off the injection sites. We do not use penicillin or any other antibiotics for this purpose, because they are specific binders. Interestingly, these two nonspecific drugs opened the window for the modern medicine.
Ueda
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Anesthesia Service and Research, VA Salt Lake City Health Care System, University of Utah School of Medicine, Salt Lake City, UT, USA. issaku.ueda@m.cc.utah.edu
D000758:Anesthesia; D000777:Anesthetics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001517:Coleoptera / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013816:Thermodynamics
D000777:Anesthetics; D004791:Enzyme Inhibitors; D007473:Ion Channels; D008156:Luciferases