TY - JOUR T1 - Do Specific or Nonspecific Interactions with Proteins Underlie Inhalational Anesthetic Action? JF - Molecular Pharmacology JO - Mol Pharmacol SP - 610 LP - 615 VL - 54 IS - 4 AU - Roderic G. Eckenhoff Y1 - 1998/10/01 UR - http://molpharm.aspetjournals.org/content/54/4/610.abstract N2 - To determine whether specific or nonspecific interactions between inhaled anesthetics and proteins are more likely to underlie anesthetic actions, analysis of hydrogen/tritium exchange was used to measure effects on the stability of two model proteins that had been previously shown to bind anesthetics specifically (bovine serum albumin) or only nonspecifically (myoglobin). The data indicated that stabilization of albumin correlated with the potencies of a wide range of anesthetic compounds significantly better than did destabilization of myoglobin. In addition, sensitivity to nonanesthetics, isoflurane stereoselectivity, and temperature and pressure effects all influenced the stabilization of bovine serum albumin, but not the destabilization of myoglobin, in a manner strongly supporting the premise that specific binding interactions with protein targets underlie anesthetic action. These observations significantly increase the likelihood that such interactions can be found and optimized. The American Society for Pharmacology and Experimental Therapeutics ER -