THE FATE OF THE OPTICAL ISOMERS OF ALPHA-ACETYLMETHADOL

¹ Department of Pharmacology, Tufts College Medical School, Boston, Mass.
² College of Pharmacy and Department of Pharmacology and Experimental Therapeutics, University of California School of Medicine, San Francisco

A modified Brodie's methyl orange technic was described for the determination of the optical isomers of -acetylmethadol in biological materials. In studies on the rat, the levo-rotatory isomer appeared to be slowly absorbed when the drug was given either perorally or subcutaneously. Only negligible amounts could be detected in the blood five minutes after intravenous injection. With all three methods of administration, the highest concentrations were found in the lung. Kidney, spleen, liver and fat usually contained appreciable levels whereas only very low levels were present in the heart, brain and blood. A large proportion of the drug was found in the carcass (chiefly muscle and bone) although the concentration of the drug was low. Considerable levels were still present in most tissues 24 hours after a single subcutaneous or intravenous injection. Concomitantly, high concentrations were found in the stomach contents but only negligible amounts were found in the feces. Biliary and urinary excretion was low. There appears to be little correlation between the observable morphine-like effects and the levels of levo-rotatory -acetylmethadol attained in the organs. Despite the rapid tissue uptake after parenteral administration, there was a delay in onset of the morphine-like effects whereas following peroral administration the actions were observed earlier even though tissue levels were lower. Although the distribution pattern of the dextro-rotatory isomer was somewhat similar, the levels in the organs were not nearly as sustained.