THE INTERRELATIONSHIPS AMONG THE CENTRAL, PERIPHERAL AND ANTICHOLINESTERASE EFFECTS OF SOME MORPHINAN DERIVATIVES

¹ Department of Pharmacology, College of Medicine, State University of Iowa, Iowa City, Iowa

In an attempt to find evidence for the frequent suggestion that the effects of the potent analgetics are related to some phase of acetylcholine metabolism, the anticholinesterase activities exhibited quantitatively by morphine, Dromoran and similar compounds were compared to the central and peripheral phenomena they present. Cholinesterases from bovine erythrocytes, rat brain, dog serum and the muscular wall of dog intestine were studied. Drugs used were morphine, codeine, nalorphine and both the d- and l-isomers of the corresponding morphinan derivatives. Effects of the drugs on intestinal tone were studied in unanesthetized dogs with Thiry-Vella loops. There was good correlation between analgesia and the intestinal tone effect, but very poor correlation between either of these effects and the pattern of inhibitions among the drugs for any of the cholinesterases studied. The more potent analgetics had a greater inhibitory effect on cholinesterase activity, but this was not proportional to the recognized analgetic activity. Furthermore, the allyl derivative in the morphinan series—an antagonist to the analgetic action of other drugs—had the greatest anticholinesterase activity. The data reported suggest that the analgesia and intestinal effects of these compounds are probably not dependent upon an anticholinesterase activity.