The minimum alveolar anesthetic concentration of 2-, 3-, and 4-alcohols and ketones in rats: Relevance to anesthetic mechanisms

Albert Won, Irene Oh, Mark Liao, James M. Sonner, R. Adron Harris, Michael J. Laster, Robert J Brosnan, James R. Trudell, Edmond I. Eger

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1419-1426
Number of pages8
JournalAnesthesia and Analgesia
Volume102
Issue number5
DOIs
StatePublished - May 2006

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Ketones
Anesthetics
Alcohols
Gases
Carbon
Oxygen
Octanols
Hydrophobic and Hydrophilic Interactions
Methanol
Oils
Water

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The minimum alveolar anesthetic concentration of 2-, 3-, and 4-alcohols and ketones in rats : Relevance to anesthetic mechanisms. / Won, Albert; Oh, Irene; Liao, Mark; Sonner, James M.; Harris, R. Adron; Laster, Michael J.; Brosnan, Robert J; Trudell, James R.; Eger, Edmond I.

In: Anesthesia and Analgesia, Vol. 102, No. 5, 05.2006, p. 1419-1426.

Research output: Contribution to journalArticle

Won, Albert ; Oh, Irene ; Liao, Mark ; Sonner, James M. ; Harris, R. Adron ; Laster, Michael J. ; Brosnan, Robert J ; Trudell, James R. ; Eger, Edmond I. / The minimum alveolar anesthetic concentration of 2-, 3-, and 4-alcohols and ketones in rats : Relevance to anesthetic mechanisms. In: Anesthesia and Analgesia. 2006 ; Vol. 102, No. 5. pp. 1419-1426.
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