The Preparation of N-Allylnormorphine

Mu Opioids and Their Receptors: Evolution of a Concept

“…1A), which is more potent than morphine. Substitutions on the nitrogen greatly influence the pharmacology of the compound, with replacement of the N-methyl group of the 4,5a-epoxymorphinans with either an N-allyl or N-methylcyclopropyl group typically converting the compound from an agonist to antagonist, as first demonstrated with N-allylnorcodeine (Von Braun, 1916) and N-allylnormorphine (nalorphine) (McCawley et al, 1941;Weijlard and Erickson, 1942;Unna, 1943) (Fig. 1A).…”

“…This discovery of the first antagonist was buried in the literature for 25 years. The next attempt to use an allyl nitrogen substitution to make an opiate free from respiratory depression came in the 1940s with the synthesis and studies of N-allyl-normorphine (nalorphine) (McCawley et al, 1941;Weijlard and Erickson, 1942;Unna, 1943). The N-allyl replacement of the N-methyl group created a new class of drugs that enabled the reversal of respiratory depression seen with morphine, but which also precipitated withdrawal in dependent subjects.…”

Kappa-opioid receptor ligands

“…The discovery of nalorphine (the N-allyl analogue of morphine) went some way to achieving this goal [1]. Nalorphine was found to be an analgesic in man [2], lacking the euphoric effects of morphine and even acting as an antagonist of morphine.…”

N-Allylnormorphine in the Treatment of Neonatal Asphyxia

“…TT is surprising that earlier and wider recognition has not been given to the possibilities of N-allylnormorphine in the prevention and treatment of neonatal asphyxia due to maternal sedation with drugs of the morphine, pethidine and amidone groups. This compound was first prepared by McCawley, Hart and Marsh (1941) and its effect in combating respiratory depression in animals was demonstrated by Unna (1943) and Hart and McCawley (1944) but little or no work was published on its effect on the human subject until Eckenhoff, Elder and King (1952), Adriani and Kerr (1953) and Fraser et al (1952) demonstrated its effectiveness in cases of poisoning due to amidone, pethidine and morphine. Eckenhoff, Hoffman and Dripps (1952) were first to describe its use in the treatment of neonatal asphyxia and since then a further large series of cases has been published by Eckenhoff, Hoffman and Funderburg (1953) who found N-allylnormorphine effective when administered intravenously to the narcotized mother 10 to 20 minutes before delivery.…”