Mechanism of anesthesia: The potency of four derivatives of octane corresponds to their hydrogen bonding capacity

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Abstract
The anesthetic potency of four derivatives of n-octane was measured by tadpole righting reflex and expressed as effective millimolar concentration of drug in membrane, ED 50 M . Potency diminished (ED50 increased) in this order: 1-octanol, ED 50 M =5.5; 1-(2-methoxyethoxy)octane, ED 50 M =28; 1-methoxyoctane, ED 50 M =61; and 1-cholorooctane, ED 50 M >100. Since the aliphatic chain length was kept constant it is concluded that the differences in anesthetic potency are a consequence of the differences in head group structure. This results is predicted by a theory (Lipids 17, 1001–1003 [1982]) which holds that anesthesia is the result of a drug-induced restructuring of the hydrogen belts, those strata of the membrane that contain the hydrogen bond receiving and donating CO and OH group of the membrane lipids and the adjoining proteins. The Meyer-Overton rule for anesthetics should be modified: chemical induce anesthesia at equimolar in-membrane concentration provided their hydrogen-bonding parts are identical.

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