POLYHALOGENATED AND PERFLUORINATED COMPOUNDS THAT DISOBEY THE MEYER-OVERTON HYPOTHESIS

Fourteen polyhalogenated, completely halogenated (perhalogenated), or perfluorinated compounds were examined for their anesthetic effects in rats. Anesthetic potency or minimum alveolar anesthetic concentration (MAC) was quantified using response/nonresponse to electrical stimula tion of the tail as the end-point. For compounds that produced excitab le behavior, and/or did not produce anesthesia when given alone, we de termined MAC by additivity studies with desflurane. Nine of 14 compoun ds had measurable MAC values with products of MAC x oil/gas partition coefficient ranging from 3.7 to 24.8 atm. Because these products excee d that for conventional inhaled anesthetics (1.8 atm), they demonstrat e a deviation from the Meyer-Overton hypothesis. Five compounds (CF3CC lFCF3, CF3CClFCClFCF3, perfluorocyclobutane, 1,2-dichloroperfluorocycl obutane, and 1,2-dimethylperfluorocyclobutane) had no anesthetic effec t when given alone, had excitatory effects when given alone, and tende d to increase the MAC for desflurane. These five compounds had no anes thetic properties in spite of their abilities to dissolve in lipids an d tissues, to penetrate into the central nervous system, and to be adm inistered at high enough partial pressures so that they should have an anesthetic effect as predicted by the Meyer-Overton hypothesis. Such compounds will be useful in identifying and differentiating anesthetic sites and mechanisms of action. Any physiologic or biophysical/bioche mical change produced by conventional anesthetics and deemed important for the anesthetic state should not be produced by nonanesthetics.