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Anaesthetics in a bind?

1997; Elsevier BV; Volume: 18; Issue: 12 Linguagem: Inglês

10.1016/s0165-6147(97)01135-8

1873-3735

John A. Peters, Jeremy J. Lambert,

Neuroscience and Neuropharmacology Research

General anaesthetics have been used as an adjunct to surgery for over 150 years, yet their mechanism of action remains somewhat unresolved. Lipid theories, emanating from the long-established correlation between anaesthetic potency and lipid solubility, purport perturbations of membrane volume or fluidity to underlie the anaesthetic state, albeit via undefined physiological actions[ 1 Franks N.P. Lieb W.R. Trends Pharmacol. Sci. 1987; 8: 169-174 Abstract Full Text PDF Scopus (135) Google Scholar ]. Such unitary theories, with nonspecific physicochemical mechanisms at their core, appear to accommodate the lack of chemical selectivity, or indeed reactivity, that characterizes certain simple anaesthetic agents. However, the credence of lipid site of action is diminished by the fact that anaesthetics, at surgical concentrations, produce only a small disruption of bilayer structure that can be mimicked by changes in temperature within the range of diurnal variation[ 1 Franks N.P. Lieb W.R. Trends Pharmacol. Sci. 1987; 8: 169-174 Abstract Full Text PDF Scopus (135) Google Scholar ]. Moreover, several clinically relevant anaesthetics, including isoflurane, barbiturates, etomidate and neuroactive steroids, act in a diastereo- or enantio-selective manner, invoking protein rather than lipid interactions[ 2 Franks N.P. Lieb W.R. Nature. 1994; 367: 607-614 Crossref PubMed Scopus (1610) Google Scholar ].