DO SPECIFIC OR NONSPECIFIC INTERACTIONS WITH PROTEINS UNDERLIE INHALATIONAL ANESTHETIC ACTION

To determine whether specific or nonspecific interactions between inha led anesthetics and proteins are more likely to underlie anesthetic ac tions, analysis of hydrogen/tritium exchange was used to measure effec ts on the stability of two model proteins that had been previously sho wn to bind anesthetics specifically (bovine serum albumin) or only non specifically (myoglobin). The data indicated that stabilization of alb umin correlated with the potencies of a wide range of anesthetic compo unds significantly better than did destabilization of myoglobin. in ad dition, sensitivity to nonanesthetics, isoflurane stereoselectivity, a nd temperature and pressure effects all influenced the stabilization o f bovine serum albumin, but not the destabilization of myoglobin, in a manner strongly supporting the premise that specific binding interact ions with protein targets underlie anesthetic action. These observatio ns significantly increase the likelihood that such interactions can be found and optimized.