Normorphine

Normorphine
Clinical data
Other names	Normorphine
Dependence; liability	High
ATC code	none;
Legal status
Legal status	AU: S9 (Prohibited substance); BR: Class A1 (Narcotic drugs); 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;
KEGG	C11785;
ChEMBL	ChEMBL1227;
CompTox Dashboard (EPA)	DTXSID1049019 ;
ECHA InfoCard	100.006.712
Chemical and physical data
Formula	C16H17NO3
Molar mass	271.316 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 ;
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Normorphine is an opiate analogue, the N-demethylated derivative of morphine, that was first described in the 1950s^[2] when a large group of N-substituted morphine analogues were characterized for activity. The compound has relatively little opioid activity in its own right,^[3]^[4] 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.^[5] with its formation from morphine catalyzed 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 grams 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

^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ Clark RL, Pessolano AA, Weijlard J, Pfister K (October 1953). "N-Substituted epoxymorphinans". Journal of the American Chemical Society. 75 (20): 4963–7. doi:10.1021/ja01116a024.
^ Fraser HF, Wikler A, Van Horn GD, Eisenman AJ, Isbell H (March 1958). "Human pharmacology and addiction liability of normorphine". The Journal of Pharmacology and Experimental Therapeutics. 122 (3): 359–69. PMID 13539761.
^ Lasagna L, De Kornfeld TJ (November 1958). "Analgesic potency of normorphine in patients with postoperative pain". The Journal of Pharmacology and Experimental Therapeutics. 124 (3): 260–3. PMID 13588540.
^ Yeh SY (January 1975). "Urinary excretion of morphine and its metabolites in morphine-dependent subjects". The Journal of Pharmacology and Experimental Therapeutics. 192 (1): 201–10. PMID 235634.
^ Projean D, Morin PE, Tu TM, Ducharme J (August 2003). "Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 33 (8): 841–54. doi:10.1080/0049825031000121608. PMID 12936704. S2CID 41467595.
^ "Quotas - 2014". DEA Diversion Control Division.

[1] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[2] Clark RL, Pessolano AA, Weijlard J, Pfister K (October 1953). "N-Substituted epoxymorphinans". Journal of the American Chemical Society. 75 (20): 4963–7. doi:10.1021/ja01116a024.

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

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

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

[6] Projean D, Morin PE, Tu TM, Ducharme J (August 2003). "Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 33 (8): 841–54. doi:10.1080/0049825031000121608. PMID 12936704. S2CID 41467595.

[7] "Quotas - 2014". DEA Diversion Control Division.

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Clinical data

Other names	Normorphine
Dependence liability	High
ATC code	none
Legal status
Legal status	AU: S9 (Prohibited substance) BR: Class A1 (Narcotic drugs)^[1] 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^Y
PubChem CID	5462508
IUPHAR/BPS	1630
ChemSpider	4575435^N
UNII	XUI1Y24IMI
KEGG	C11785
ChEMBL	ChEMBL1227
CompTox Dashboard (EPA)	DTXSID1049019
ECHA InfoCard	100.006.712
Chemical and physical data
Formula	C₁₆H₁₇NO₃
Molar mass	271.316 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^N Key:ONBWJWYUHXVEJS-ZTYRTETDSA-N^N
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