RAT TISSUE LEVELS OF CARBON-14 LABELED ANALGETICS AS RELATED TO PHARMACOLOGICAL ACTIVITY

¹ Department of Pharmacology and Experimental Therapeutics, University of California, School of Medicine and College of Dentistry, San Francisco 22, California

The concentrations of carbon-14 labeled morphine, codeine and methadone in the central nervous system and other tissues of the rat were determined at intervals after drug administration. Peak levels in the central nervous system correlated with pharmacological activity as measured by the pain reaction time method. Kidney and liver levels correlated with the major routes of excretion for each agent. Countercurrent distribution studies indicated that unaltered codeine and methadone were present in the central nervous system 30 min. after drug administration. Liver and bile from methadone^* treated rats contamed^* at least two carbon-14 labeled metabolites as well as unchanged methadone^*. Radioautographs of tissues from a morphine^* treated rat showed concentration of activity in the choroid plexus and ventricles of the brain, some differential distribution in kidney and liver and uniform distribution in other tissues studied.