Nalorphine (N-Allylnormorphine)

Abstract

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.

The opioid receptor: emergence through millennia of pharmaceutical sciences

“…Ultimately the community gave credit to Wood for introducing the technique and Hunter for establishing a systemic action needle (10). Another example of early recognition of the potential benefit of direct delivery to the presumptive site of opioid action was the first local spinal injections (12), initially of cocaine, in 1885 by Leonard Corning. In 1899-1901, morphine mixed with cocaine or other local anesthetic was delivered spinally by physicians on three separate continents including Dr. Matas of New Orleans (13), Dr. N. Racoviceanu-Pitesti of Romania ( 14), and Dr. Otojiro Kitagawa of Japan (15).…”

“…N-Allyl-opioids: The first demonstration of antagonism of morphine by another opioid is uniformly attributed to the work of a German chemist, J. Pohl, published in 1915 (12,18). Pohl was reportedly interested in the observation of a colleague who had decided that allyl compounds stimulated the respiratory system.…”

“…Pohl was reportedly interested in the observation of a colleague who had decided that allyl compounds stimulated the respiratory system. Pohl theorized that by adding an allyl group to opioid alkaloids, the effects of opioids on the nervous system may be countered (12). He then observed that his synthetic product of N-allylnorcodeine reversed the respiratory depression induced by morphine in rabbit and dog (12,18).…”

“…Pohl theorized that by adding an allyl group to opioid alkaloids, the effects of opioids on the nervous system may be countered (12). He then observed that his synthetic product of N-allylnorcodeine reversed the respiratory depression induced by morphine in rabbit and dog (12,18). This monumental observation of millennial importance heralded the introduction of a potential antidote for the lethal effects of opium, a key constituent of a mixture (Mithridatium) that was originally intended to serve as an antidote to poison itself.…”

Similarity Between Receptors Responsible for the Production of Analgesia and Lenticular Opacity

“…Furthermore, the ratios for the activity of one isomer to that of the other were constant for the two actions. Nalorphine antagonism Nalorphine is generally believed to reduce or prevent the analgesic action of morphine-like drugs by competing successfully for the receptor involved (Lasagna, 1954;Seibert & Huggins, 1953;Landmesser, Cobb & Converse, 1953).…”