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The membrane concentrations of alcohol anesthetics

Biochimica et Biophysica Acta (BBA) - Biomembranes
Publication Date
DOI: 10.1016/0005-2736(71)90210-0
  • Biology
  • Pharmacology


Abstract 1. 1. This work provides evidence for the Overton-Meyer partition theory of anesthesia. This theory states that the cell membrane anesthetizing concentration is of the order of 0.03 molal (moles of anesthetic per kg membrane). The membrane concentrations found experimentally for alcohols ranged from 0.01 molal for decanol to 0.04 Molal for pentanol in hemoglobin-free erythocyte ghost membranes at concentrations which are 25% effective in protecting erythrocyte membranes, and which are also effective in stabilizing nerve fibers. Since the membrane concentration decreased linearly with chain length by a factor of about one-third on going from pentanol to decanol, the pharmacological intrinsic efficacy of decanol (in the membrane phase) is 3.2 times greater than that of pentanol. 2. 2. The decrease in membrane concentration ( c membrane ) with increasing chain length of the alcohols indicated that some size-dependent parameter of the anesthetic was important in determining the final amount of membrane stabilization. Mullins 19 had predicted that such a parameter should exist and suggested that it is the volume of the anesthetic molecule, V mol . The data support this insofar as V mol ·c membrane is almost the same for all the alkanols. The data also support, however, a new hypothesis which states that the membrane concentration should be corrected by δF, the free energy of binding, since this parameter is possibly the most general index of the “extensive” influence of the anesthetic in the drug-receptor interaction. The value for ΔF·c membrane was of the order of 60 cal/kg membrane for each alkanol. 3. 3. The mean free energy of alcohol adsorption was −695 ± 81 (S.E.) cal/mole of methylene groups, indicating that the membrane-alcohol interaction was hydrophobic. 4. 4. Assuming an unlimited number of membrane binding sites, the membrane/buffer partition coefficients could be averaged; the mean values were 3·4 for pentanol, 39 for heptanol, 152 for octanol, 582 for nonanol, and 1226 for decanol. Assuming there was only a finite number of binding sites, the mean for the maximum number of alcohol binding sites was computed to be 65.5 mmoles of alkanol per kg of dry membrane.

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