Anesthetic potencies of secondary alcohol enantiomers.
The Meyer-Overton rule has been interpreted to mean that general anesthetics act at a nonpolar site, either in a lipid bilayer or a protein. Optical isomers, also called enantiomers, are pairs of compounds with the same molecular formula and functional groups, but which differ in the arrangement of the groups around an "asymmetric" carbon atom and in the direction they rotate plane-polarized light. By definition, enantiomers that are anesthetics can distinguish between stereoselective and nonselective sites of anesthetic action. We used such enantiomers to determine whether anesthetics are stereoselective in their actions on animals by measuring the potencies of a homologous series of secondary aliphatic alcohols from 2-butanol through 2-octanol in tadpoles, using reversible loss of righting reflex as the endpoint. None of the isomeric pairs exhibited significant differences in potency. Anesthetic potency increased logarithmically with the number of carbon atoms in the hydrocarbon chain of the alcohol. The ED50 +/- SE (mM) for the (+) and (-) forms of the alcohols, respectively, were as follows: 2-butanol 17 +/- 1.2, 17 +/- 1.1; 2-pentanol 4.7 +/- 0.28, 4.8 +/- 0.27; 2-hexanol 1.33 +/- 0.068, 1.42 +/- 0.079; 2-heptanol 0.32 +/- 0.011, 0.33 +/- 0.020; and 2-octanol 0.063 +/- 0.0042, 0.061 +/- 0.0032. These data demonstrate a lack of stereoselectivity in the interactions between the anesthetic secondary alcohols and their site of action in animals.
D020003:1-Octanol; D000768:Anesthesia, General; D000818:Animals; D000440:Butanols; D004305:Dose-Response Relationship, Drug; D000441:Hexanols; D000442:Octanols; D011894:Rana pipiens; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000440:Butanols; D000441:Hexanols; D000442:Octanols; C043958:2-butanol; C037076:2-hexanol; D020003:1-Octanol