The anesthetic potencies of alkanethiols for rats: Relevance to theories of narcosis

Meyer and Overton suggested that anesthetic potency correlates inversely wi th lipophilicity. Thus, MAC times the olive oil/gas partition coefficient e quals an approximately constant value of 1.82 +/- 0.56 atm (mean +/- SD). M AC is the minimum alveolar concentration of anesthetic required to eliminat e movement in response to a noxious stimulus in 50% of subjects. Although M AC times the olive oil/gas partition coefficient also equals an approximate ly constant value for normal alkanols from methanol through octanol, the va lue (0.156 +/- 0.072 atm) is 1/10th that found for conventional anesthetics . We hypothesized that substitution of sulfur for the oxygen in n-alkanols would decrease their saline/gas partition coefficients (i.e., decrease pola rity) while sustaining lipid/gas partition coefficients. Further, we hypoth esized that these changes would produce products of MAC times olive oil par tition coefficients that approximate those of conventional anesthetics. To test these predictions, we measured MAC in rats, and saline and olive oil s olubilities for the series H(CH2)(n)SH, comparing the results with the seri es H(CH2)(n)OH for compounds having three to six carbon atoms. As hypothesi zed, the alkanethiols had similar oil/gas partition coefficients, 1000-fold smaller saline gas partition coefficients, and MAC values 30 times greater than for comparable alkanols. Such findings are consistent with the notion that the greater potency of many alkanols (greater than would be predicted from conventional inhaled anesthetics and the Meyer-Overton hypothesis) re sults from their greater polarity.