The Minimum Alveolar Anesthetic Concentration of 2-, 3-, and 4-Alcohols and Ketones in Rats: Relevance to Anesthetic Mechanisms

Abstract

The Meyer-Overton hypothesis predicts that anesthetic potency correlates inversely with lipophilicity; e.g., MAC times the olive oil/gas partition coefficient equals a constant of approximately 1.82 +/- 0.56 atm (mean +/- sd) for conventional inhaled anesthetics. MAC is the minimum alveolar concentration of anesthetic required to eliminate movement in response to a noxious stimulus in 50% of subjects. In contrast to conventional inhaled anesthetics, MAC times the olive oil/gas partition coefficient for normal alcohols from methanol through octanol equals a constant one tenth as large as that for conventional inhaled anesthetics. The alcohol (C-OH) group causes a great affinity of alcohols to water, and the C-OH may tether the alcohol at the hydrophobic-hydrophilic interface where anesthetics are thought to act. We hypothesized that the position of the C-OH group determined potency, perhaps by governing the maximum extent to which the acyl portion of the molecule might extend into a hydrophobic phase. Using the same reasoning, we added studies of ketones with similar numbers of carbon atoms between the C=O group and the terminal methyl group. The results for both alcohols and ketones showed the predicted correlation, but the correlation was no better than that with carbon chain length regardless of the placement of the oxygen. The oil/gas partition coefficient predicted potency as well as, or better than, either chain length or oxygen placement. Hydrophilicity, as indicated by the saline/gas partition coefficient, also seemed to influence potency.

Chirality in Anesthesia II: Stereoselective Modulation of Ion Channel Function by Secondary Alcohol Enantiomers

“…Racemic alcohols were prepared from equal parts of each stereoisomer. The applied alcohol concentrations (16 mM 2-butanol; 4 mM 2-pentanol; and 2 mM 2-hexanol) are close to the blood alcohol concentrations measured at MAC in rats (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Alcohol vapor concentrations in equilibrium with perfusate were determined at the end of each experiment using headspace gas chromatography with a Carbowax column (Series 580; Gow-Mac, Bethlehem, PA), from which solution concentrations were calculated using previously determined Ostwald saline-gas partition coefficients at room temperature (11).…”

Effect of Anesthetic Structure on Inhalation Anesthesia: Implications for the Mechanism

“…In the supplementary Table S1 are given published MAC data1–8, 11–22 for a total of 150 inhaled anesthetic compounds for rats; the SMILES nomenclature for the 150 compounds is given in Table S2. We use log (1/MAC) in Table S1 because the larger is log (1/MAC) the more potent is the anesthetic.…”

Mathematical Correlations for Gas‐to‐Olive Oil, Gas‐to‐Saline Solution, and Saline Solution‐to‐Olive Oil Partition Coefficients Based on the Goss Modified Abraham Model

“…b Olive oil partition coefficient data from Ref. [29]. c Olive oil partition coefficient data from Ref.…”