Normorphine

Normorphine
Clinical data
Other names	Normorphine
ATC code	none;
Legal status
Legal status	AU: S9 (Prohibited substance); US: Schedule I;
Identifiers
	IUPAC name 3,6α-Dihydroxy-4,5α-epoxy-7,8-didehydromorphinan;
CAS Number	466-97-7 ;
PubChem CID	5462508;
IUPHAR/BPS	1630;
ChemSpider	4575435 ;
UNII	XUI1Y24IMI;
CompTox Dashboard (EPA)	DTXSID1049019 ;
ECHA InfoCard	100.006.712
Chemical and physical data
Formula	C16H17NO3
Molar mass	271.311 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c1cc(c2c3c1C[C@@H]4[C@H]5[C@]3(CCN4)[C@@H](O2)[C@H](C=C5)O)O;
	InChI InChI=1S/C16H17NO3/c18-11-3-1-8-7-10-9-2-4-12(19)15-16(9,5-6-17-10)13(8)14(11)20-15/h1-4,9-10,12,15,17-19H,5-7H2/t9-,10+,12-,15-,16-/m0/s1 ; Key:ONBWJWYUHXVEJS-ZTYRTETDSA-N ;
	(what is this?) (verify)

Normorphine is an opiate analogue, the N-demethylated derivative of morphine, that was first described in the 1950s^[1] when a large group of N-substituted morphine analogues were characterized for activity.

Normorphine has relatively little opioid activity in its own right,^[2]^[3] but is a useful intermediate which can be used to produce both opioid antagonists such as nalorphine, and also potent opioid agonists such as N-phenethylnormorphine.^[4] It is also produced as a major metabolite of morphine,^[5] with its formation from morphine catalysed by the liver enzymes CYP3A4 and CYP2C8.^[6]

Normorphine is a controlled substance listed under the Single Convention On Narcotic Drugs 1961 and the laws in various states implementing it; for example, in the United States it is a Schedule I Narcotic controlled substance, with an ACSCN of 9313 and an annual aggregate manufacturing quota of 18 grammes in 2013, unchanged from the prior year.

References

^ Journal of the American Chemistry Society 75,4963 (1953)
^ Fraser HF, Wikler A, Van Horn GD, Eisenman AJ, Isbell H. Human pharmacology and addiction liability of normorphine. Journal of Pharmacology and Experimental Therapeutics. 1958 Mar;122(3):359-69. PMID 13539761
^ Lasagna L, De Kornfeld TJ. Analgesic potency of normorphine in patients with postoperative pain. Journal of Pharmacology and Experimental Therapeutics. 1958 Nov;124(3):260-3. PMID 13588540
^ Daniel Lednicer. Central Analgetics. (1982), p146. ISBN 0-471-08314-3
^ Yeh SY. Urinary excretion of morphine and its metabolites in morphine-dependent subjects. Journal of Pharmacology and Experimental Therapeutics. 1975 Jan;192(1):201-10. PMID 235634
^ Projean D, Morin PE, Tu TM, Ducharme J. Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes. Xenobiotica. 2003 Aug;33(8):841-54. PMID 12936704

[1] Journal of the American Chemistry Society 75,4963 (1953)

[2] Fraser HF, Wikler A, Van Horn GD, Eisenman AJ, Isbell H. Human pharmacology and addiction liability of normorphine. Journal of Pharmacology and Experimental Therapeutics. 1958 Mar;122(3):359-69. PMID 13539761

[3] Lasagna L, De Kornfeld TJ. Analgesic potency of normorphine in patients with postoperative pain. Journal of Pharmacology and Experimental Therapeutics. 1958 Nov;124(3):260-3. PMID 13588540

[4] Daniel Lednicer. Central Analgetics. (1982), p146. ISBN 0-471-08314-3

[5] Yeh SY. Urinary excretion of morphine and its metabolites in morphine-dependent subjects. Journal of Pharmacology and Experimental Therapeutics. 1975 Jan;192(1):201-10. PMID 235634

[6] Projean D, Morin PE, Tu TM, Ducharme J. Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes. Xenobiotica. 2003 Aug;33(8):841-54. PMID 12936704

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