Open AccessEffect of n-Alkane Kinetics in Rats on Potency Estimations and the Meyer-Overton Hypothesis
Author(s) -
Jin Liu,
Michael J. Laster,
Shahram Taheri,
Edmond I. Eger,
Ben S. Chortkoff,
Michael J. Halsey
Publication year - 1994
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - English
Resource type - Journals
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/00000539-199412000-00005
Subject(s) - potency , medicine , kinetics , alkane , pharmacology , biochemistry , in vitro , chemistry , physics , quantum mechanics , catalysis
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 might be that a large difference in inspired-to-arterial partial pressure exists, i.e., that the inspired partial pressure misrepresents the effective partial pressure. To test this explanation, we investigated the kinetics of five consecutive even-numbered n-alkanes (C2H6 to C10H22) in rats. The ratio of end-tidal-to-inspired (PA/PI), arterial-to-end-tidal (Pa/PA), and arterial-to-inspired (Pa/PI) partial pressures decreased with increasing carbon chain length, consistent with our separate finding that blood solubility increased. Using Pa/PI and the minimum inspired concentration (MIC) obtained previously, we calculated the true effective potency, minimum alveolar anesthetic concentration (MAC); of these n-alkanes as (Pa/PI)(MIC). This markedly improved, but did not perfectly correct, the correlation of MAC with lipid solubility (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 conventional anesthetics was -1.046 (approached-1.0). These data imply that olive oil does not adequately mimic the nature of the anesthetic site of action of n-alkanes.