Normorphine

Normorphine
Clinical data
Other names	Normorphine
ATC code	none;
Legal status
Legal status	AU: S9 (Prohibited substance); CA: Schedule I; DE: Anlage I (Authorized scientific use only); 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 2014, unchanged from the prior year. The salts in use are the free base hexahydrate (free base conversion ratio 0.715), and hydrochloride (0.833).^[7]

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
^ http://www.deadiversion.usdoj.gov/fed_regs/quotas/2014/fr0825.htm

[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

[7] ttp://www.deadiversion.usdoj.gov/fed_regs/quotas/2014/fr0825.htm

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