ANTAGONISTIC EFFECT OF N-ALLYL-NORMORPHINE UPON MORPHINE

¹ From the Merck Institute for Therapeutic Research, Rahway, New Jersey

A comparison of the effects obtained with N-allyl-normorphine and with morphine shows that N-allyl-normorphine is about as toxic, but much less effective than morphine in raising the threshold for pain in mice. In contrast to morphine small doses do not depress the respiration; very large doses, however, cause arrest of the respiration, and all animals succumbing to N-allyl-normorpine die of respiratory failure.

N-allyl-normorphine prevents or abolishes the action of morphine. Premedication with this substance increases the resistance of mice to morphine so that otherwise lethal doses are tolerated without untoward effects. Furthermore, an injection of N-allyl-normorphine prior to that of morphine prevents analgesia (mice), respiratory depression (rabbits), and the general depressing (dogs) and stimulatory (cats) effects as well.

If morphine is administered in the first place, a subsequent injection of N-allyl-normorphine abolishes its analgesic effect (mice) restores the depressed respiration to its previous level (rabbits) and abolishes its toxic manifestations in cats and dogs. The reduction in the mortality of morphine poisoning in mice by N-allyl-normorphine further demonstrates the effectiveness of this substance as an antidote against morphine.

Since the site of action of morphine is generally assumed to be central, it would appear that N-allyl-normorphine by virtue of its chemical relationship to morphine exerts its action upon the same centers as morphine rendering them less sensitive to morphine. This assumption would offer the most plausible explanation for the observations reported.

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