MORPHINE ANTAGONISTS. I. THE DISTRIBUTION AND EXCRETION OF MORPHINE-C¹⁴ IN THE PRESENCE OF N-ALLYL NORMORPHINE AND 5-AMINOACRIDINE

¹ Department of Pharmacology, University of Chicago, Chicago, Illinois

The administration of N-allyl normorphine 25 mgm./kgm. or 5-aminoacridine 2.5 mgm./kgm. to mice previously given 10 mgm./kgm. morphine-C¹⁴ (54,400 cpm./20 gm. body weight) produces marked changes in distribution and excretion of radioactivity. All tissues examined are affected to a greater or lesser degree, but special reference is made to liver, kidney, small intestine and urine. NANM-treated animals accumulate radioactivity in bladder urine at approximately the same rate as controls, but void within two hours following administration of morphine and antagonist. The percentage injected dose excreted by control mice is approximately equal at 6 hours to that excreted by the NANM-treated group at the end of two hours. 5-Aminoacridine also facilitates the excretion of radioactivity following doses of morphine-C14, and appears to be more active in this respect than NANM. Furthermore, the distribution pattern of 5AA presents certain differences from those observed in the presence of NANM, indicating a possibly different mode of action. The possibility that both these antagonists alter the free:bound morphine ratio in urine has been suggested by the distribution data and is being investigated at this time.