To the Editor:-I read with great interest and enjoyment the recent contribution of Forman and Raines whose data add to a body of information demonstrating that lipid solubility is a necessary, but not sufficient, physical correlate of anesthetic potency. It is always useful to go back in history and demonstrate that plus ca change … because nearly a quarter of a century ago, Nahrwold, Clark, and I demonstrated that biological function, i.e., depression of mitochondrial respiration, could more precisely predict ability to perturb the central nervous system than the physical characteristic of lipid solubility. Analogous to the current study, we found that highly lipophilic compounds that had no effect on the central nervous system were also devoid of inhibitory effect on mitochondrial respiration. These findings were not completely specific: hexafluorodiethyl ether depressed mitochondrial respiration but produced convulsions rather than “anesthesia,” whereas its isomer, hexafluoroisopropyl methyl ether, was associated with both mitochondrial depression and anesthesia. 
I wonder whether Forman and Raines have any data regarding the ability of their elegant preparations to distinguish between the two central nervous system activities of anesthesia and convulsions? Such findings would be useful in the further formulation of a predictive in vitro model for the anesthetic state.
Peter J. Cohen, M.D., J.D.
Special Expert; National Institute on Drug Abuse; Bethesda, Maryland 20892;email@example.com
(Accepted for publication October 12, 1998.)