Concentrations of anesthetics across the water-membrane interface; the
Meyer-Overton hypothesis revisited
Andrew, Pohorille,
Michael A. Wilson,
Michael H. New,
and Christophe Chipot
Exobiology
Branch
NASA -- Ames Research Center
MS 239-4
Moffett Field, California 94035-1000
Department
of Pharmaceutical Chemistry,
University of California, San Francisco,
San Francisco, California 94143
current
address:
Laboratoire de Chimie Théorique,
Unité de Recherche Associée au CNRS n
510,
Université Henri Poincaré-Nancy I, BP. 239,
54506 Vand
uvre-lès-Nancy
Cedex - France
corresponding author
Abstract:
The free energies of transferring a variety of anesthetic and
nonanesthetic compounds across water-oil and water-membrane interfaces were computed using
computer simulations. Anesthetics exhibit greatly enhanced concentrations at these
interfaces, compared to nonanesthetics. The substitution of the interfacial solubilites of
the anesthetics for their bulk lipid solubilities in the Meyer-Overton relation, was found
to give a better correlation, indicating that the potency of an anesthetic is directly
proportional to its solubility at the interface.
