EFFECT OF N-ALKANE KINETICS IN RATS ON POTENCY ESTIMATIONS AND THE MEYER-OVERTON HYPOTHESIS

Neither lipophilicity nor vapor pressure of larger n-alkanes appear to correlate with their anesthetizing partial pressures in inspired gas. Such results suggest that the Meyer-Overton hypothesis and Ferguson's rule may not apply to these compounds. An alternative explanation mig ht be that a large difference in inspired-to-arterial partial pressure exists, i.e., that the inspired partial pressure misrepresents the ef fective partial pressure. To test this explanation, we investigated th e kinetics of five consecutive even-numbered n-alkanes (C2H6 to C10H22 ) in rats. The ratio of end-tidal-to-inspired (P-A/P-I), arterial-to-e nd-tidal (P-a/P-A), and arterial-to-inspired (P-a/P-I) partial pressur es decreased with increasing carbon chain length, consistent with our separate finding that blood solubility increased. Using P-a/P-I and th e minimum inspired concentration (MIC) obtained previously, we calcula ted the true effective potency, minimum alveolar anesthetic concentrat ion (MAC); of these n-alkanes as (P-a/P-I)(MIC). This markedly improve d, but did not perfectly correct, the correlation of MAC with lipid so lubility (the Meyer-Overton hypothesis) and vapor pressure (Ferguson's rule). A coefficient of variation of 76.7% was found for the product of MAC and the olive oil/gas partition coefficient. More importantly, the correlation of the logarithm of MAC and oil solubility had a slope of -0.724 (i.e., deviated from -1.0), whereas the slope for eight con ventional anesthetics was -1.046 (approached -1.0). These data imply t hat olive oil does not adequately mimic the nature of the anesthetic s ite of action of n-alkanes.