N-Allylnormorphine

Nalorphine Nalorphine, N-allylnormorphine (3.1.75), is synthesized from morphine by its complete acetylation, i.e. by transformation into heroin (3.1.21), in order to temporarily protect the hydroxyl groups, and then by undergoing demethylation. In order to do this, heroin (3.1.21) is processed with cyanogen bromide. The resulting N-cyano derivative (3.1.73) is hydrolyzed by a solution of hydrochloric acid into the N-demethylated morphine, normorphine (3.1.74), whose secondary amine group undergoes alkylation with allylbromide to give desired nalorphine [47,48]. 

Nalorphine (11 N-allylnormorphine Fig. 11.4) [31] was found to antagonize the properties of morphine, and was utilized as an antidote for morphine poisoning,... 

N-Allylnormorphine (Nalorphine) was prepared(143) in impure form<144) in 1941 for evaluation as an analgesic with low respiratory depression properties, but powerful morphine antagonist activity was observed, and subsequently this has been exploited extensively in the clinic/144,145 ... 

Bentley KW, Hardy DG (1967) Novel analgesics and molecular rearrangements in the morphine-thebaine group. 3. Alcohols of the 6,14-endo-ethenotetrahydrooripavine series and derived analogs of N-allylnormorphine and -norcodeine. J Am Chem Soc 89 3281-3292... 

Nalorphine Dinicotinate. 7,8-Didehydro-4,5-epoxy-t7-(2-propenyl>morphtnan-3,6-diol bis(3-pyridine-corboxylatel (ester) N-allylnormorphine dinicotinate bis-(nicotinic acid) diester of N-allylnormorphine N-ally I normorphine bisfpyridine-3-carboxylic acid) ester nalorphine bis(nlcotlnate) Nimelan. CjjH N.Oj mo] wt 521.55. C 71.39%, H 5.22%, N 8,06%, O 15.34%. Prepn Pongratz, Zirm, Afonatsh. 91, 396 (1960). 

Brochmann-Hanssen, E. and Cheng, C. Y. (1984) Biosynthesis of a narcotic antagonist conversion of N-allylnorreticuline to n-allylnormorphine in Papaver somniferum. J. Nat. Prod. 47, 175,176. 

Abstinence syndromes could be induced after the subcutaneous injection of 15 mg. of N-allylnormorphine as early as 1 week after experimental addiction to morphine 15 mg. or methadone 10 mg. four times daily. The syndrome was recognized by the subjects themselves, who nicknamed the... 

Three of the four subjects on the methadone study refused to continue with the experiments, an event which rarely happens at the U.S. Public Health Service laboratory in Lexmgton, Kentucky, after they had experienced the abstinence syndrome precipitated by iV-allylnormorphine. The acute syndrome precipitated by IV-allylnormorphine in methadone addicts contrasts strikingly with the mild changes which are observed after abrupt withdrawal of methadone. The subjects who refused to continue with the methadone study exhibited only lethargy, anorexia, and irritability during the first week after abrupt termination of methadone administration. N-Allylnormorphine failed to precipitate abstinence phenomena 3 days after completion of withdrawal of methadone by rapid reduction in the subject who continued with the study. 

In 1915, it was shown that N-allylnorcodeine abolished both heroine- and morphine-indueed respiratory depression. Almost 25 years later (1940), it was observed that N-allylnormorphine (eom-monly known as nalorphine) possessed more marked and signifieant morphine antagonizing aetions. Thirteen years later (1953), it was demonstrated that nalorphine had the ability to arrest severe abstinence syndromes in postaddicts who were earlier treated briefly with either morphine, methadone or heroine. Examples of narcotic antagonists include nalorphine hydrochloride naloxone hydrochloride propiram fnmarate and pentazocine. 

Chemical Name 7,8-didehydro-4,5-epoxy-17-(2-propenyl)morphinan-3,6-diol Common Name N-allylnormorphine Structural Formula ... 

Brochmann-Hanssen E, Cheng CY (1984) Biosynthesis of a narcotic antagonist. Conversion of N-allylnorreticuline to N-allylnormorphine in Papaver somniferum. J Nat Prod 47 175-176 Brochmann-Hanssen E, Furuya T (1964) A new opium alkaloid. Isolation and characterization of ( )-l-(3 -hydroxy-4 -methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-l,2,3,4-tetrahydro-isoquinoline [( )-reticuline]. Planta Med 12 328-333 Brochmann-Hanssen E, Nielsen B (1965) (+)-Reticuhne - a new opium alkaloid. Tetrahedron Lett 1271-1274... 

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