title: Chirality in anesthesia I: minimum alveolar concentration of secondary alcohol enantiomers.
abstract: Most studies of chirality in inhaled anesthetic action have used the enantiomers of isoflurane. These enantiomers are expensive and scarce, which limits studies, such as the preliminary identification of molecular targets of anesthetic action, that can be performed with these isomers. We hypothesized that secondary alcohols (i.e., compounds having a -CH2-CHOH-CH3 group) that are experimental anesthetics would show enantioselectivity. To test this hypothesis, we determined the minimum alveolar anesthetic concentration (MAC) of the enantiomers of the homologous series of 2-alcohols from 2-butanol to 2-heptanol in rats. Because these alcohols are partially metabolized to 2-ketones during the course of study (i.e., having a -CH2-CO-CH3 group), we independently measured the MAC of the 2-ketones. Assuming additivity of MAC of the ketones with the alcohols, we corrected for the anesthetic effect of the ketones in rats to determine the MAC of the alcohols. We found that the 2-butanol and 2-pentanol isomers were enantioselective. S-(+)-2-butanol had a MAC that was 17% larger than for the R-(-)-enantiomer, whereas S-(+)-2-pentanol had a MAC that was 38% larger than the R-(-)- enantiomer. No stereoselectivity was observed for 2-hexanol and 2-heptanol. These findings may permit studies of chirality in anesthesia, particularly in in vitro systems where metabolism does not occur, using inexpensive volatile compounds.
authors.affiliation: Department of Anesthesia and Perioperative Care, S-455, University of California, San Francisco, California 94143-0464, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Won
authors.forename: Irene
authors.initials: I
authors.lastname: Oh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
authors.forename: John
authors.initials: J
authors.lastname: Popovich
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
authors.forename: James M
authors.initials: JM
authors.lastname: Sonner
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000493:pharmacokinetics*; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D000440:Butanols / Q000737:chemistry / Q000493:pharmacokinetics; D019850:Heptanol / Q000737:chemistry / Q000493:pharmacokinetics; D000441:Hexanols / Q000737:chemistry / Q000493:pharmacokinetics; D007536:Isomerism; D007659:Ketones / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000438:Alcohols; D018685:Anesthetics, Inhalation; D000440:Butanols; D000441:Hexanols; D007659:Ketones; D019850:Heptanol