HISTORY THE HISTORY of N-substituted allyl compounds of the morphine series is both fascinating and instructive. Pohl,1 almost 40 years ago, became interested in the work of a colleague named Piazza. The latter worker had found allyl compounds to be, in general, irritating to tissues and (under some circumstances) productive of stimulant effects on the respiration. Pohl reasoned that this "stimulant" or "irritant" effect might be "directed towards the central nervous system" by incorporating an allyl group into the opium alkaloids. He accordingly experimented with O-allylnormorphine and N-allylnorcodeine. Investigations in rabbits revealed that the latter drug, while essentially inactive per se, would antagonize the respiratory depression of morphine in rabbit and dog. For over 25 years this exciting fact Structural formula of morphine and of nalorphine (N-allylnormorphine). lay buried in the literature. In 1941, McCawley, Hart, and Marsh2 synthetized what they thought to be N-allylnormorphine ( Figure), in a search for a morphine derivative possessing analgesic and narcotic potency but devoid of depressant effect on the respiration. In the same year Hart3 reported the ability of this preparation to antagonize the respiratory depression of morphine.