PROPOFOL AND ETHANOL PRODUCE ADDITIVE HYPNOTIC AND ANESTHETIC EFFECTSIN THE MOUSE

The sedative and anesthetic effects of ethanol and propofol when these drugs are coadministered are not known. Accordingly, we investigated the nature of the pharmacological interaction between ethanol and prop ofol during hypnosis and anesthesia in the mouse. Propofol, ethanol, a nd mixtures of the two were administered through the tail vein in male CD-1 mice (n = 162). The loss of righting response occurring 10 s aft er injection and persisting at least 10 s thereafter was defined as hy pnosis, and lack of a motor response to tail clamping 60 s after injec tion was defined as anesthesia. The 50% effective dose (ED(50)) values for the hypnotic and anesthetic actions of the drugs were determined with quantal dose-response curves, using probit analysis. The pharmaco logical interactions were identified by the locations of ED(50) values on their corresponding hypnosis and anesthesia isoboles. For each dru g alone, the hypnotic and anesthetic ED(50) values with 0.95 confidenc e intervals were 16.70 (11.98, 23.20) mg/kg and 25.02 (20.27, 31.29) m g/kg for propofol and 0.88 (0.81, 0.95) g/kg and 1.80 (1.45, 2.23) g/k g for ethanol, respectively. For the drugs in combination, the ED(50) values for hypnosis with 0.95 confidence intervals were 6.98 (6.50, 7. 49) mg/kg propofol with 0.61 (0.57, 0.66) g/kg ethanol, and for anesth esia were 10.55 (9.76, 11.42) mg/kg propofol with 0.93 (0.86, 1.05) g/ kg ethanol, respectively. When plotted isobolographically, we found th ese combinations to be behaviorally additive both for hypnosis and ane sthesia. Although a finding of synergism would have excluded the possi bility of an identical mechanism of action for the drugs, elucidation of the molecular basis of the additivity must await further studies.