Meyer-Overton reforged: The origins of alcohol and anesthetic potency in membranes as determined by a new NMR partitioning probe, benzyl alcohol

Conference · Wed Jan 01 00:00:00 EST 1992 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:7159934

Janes, N; Ma, L; Hsu, J W; Rubin, E; Taraschi, T F ^[1]

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1. Thomas Jefferson Univ., Philadelphia, PA (United States)

The Meyer-Overton hypothesis--that anesthesia arises from the nonspecific action of solutes on membrane lipids--is reformulated using colligative thermodynamics. Configurational entropy, the randomness imparted by the solute through the partitioning process, is implicated as the energetic driving force that pertubs cooperative membrane equilibria. A proton NMR partitioning approach based on the anesthetic benzyl alcohol is developed to assess the reformulation. Ring resonances from the partitioned drug are shielded by 0.2 ppm and resolved from the free, aqueous drug. Free alcohol is quantitated in dilute lipid dispersions using an acetate internal standard. Cooperative equilibria in model dipalmitoyl lecithin membranes are examined with changes in temperature and alcohol concentration. The L[sub [beta][prime]] [yields] P[sub [beta][prime]] equilibrium has a small thermal entropy change, and, as predicted, is very sensitive to perturbation by the alcohol. The thermal entropy change of the P[sub [beta][prime]] [yields] L[sub [alpha]] is much larger and the equilibrium is insensitive. Analysis of liposomes composed of liver-microsome lipid-extracts and by contrast the dramatic effects induced by chronic ethanol-feeding further supports the utility of the technique and thermodynamic model.

• OSTI ID: 7159934
• Report Number(s): CONF-9202109-; CODEN: FAJOEC
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 6:1; Conference: American Society for Biochemistry and Molecular Biology and Biophysical Society joint meeting, Houston, TX (United States), 9-13 Feb 1992; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BENZYL ALCOHOL
METABOLISM
ANESTHETICS
CELL MEMBRANES
LIPIDS
LIPOSOMES
NMR SPECTRA
THERMODYNAMICS
ALCOHOLS
AROMATICS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HYDROXY COMPOUNDS
MEMBRANES
ORGANIC COMPOUNDS
SPECTRA
560300* - Chemicals Metabolism & Toxicology