Hydromorphinol

Hydromorphinol
Clinical data
Trade names	Numorphan
Other names	Hydromorphinol,; 14-hydroxy-7,8-dihydromorphine,; RAM-320
ATC code	none;
Legal status
Legal status	AU: S8 (Controlled drug); BR: Class A1 (Narcotic drugs); CA: Schedule I; DE: Anlage I (Authorized scientific use only); US: Schedule I;
Identifiers
	IUPAC name (5α,6α)-3,6,14-Trihydroxy-4,5-epoxy-17-methylmorphinan;
CAS Number	2183-56-4 ; 2190-27-4;
PubChem CID	5463858;
ChemSpider	4576407 ;
UNII	1O00P9X5C1;
KEGG	D12686 ;
ChEMBL	ChEMBL1951706 ;
CompTox Dashboard (EPA)	DTXSID30176242 ;
ECHA InfoCard	100.016.878
Chemical and physical data
Formula	C17H21NO4
Molar mass	303.358 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN1CC[C@]23[C@@H]4[C@H](CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O)O;
	InChI InChI=1S/C17H21NO4/c1-18-7-6-16-13-9-2-3-10(19)14(13)22-15(16)11(20)4-5-17(16,21)12(18)8-9/h2-3,11-12,15,19-21H,4-8H2,1H3/t11-,12+,15-,16-,17+/m0/s1 ; Key:AABLHGPVOULICI-BRJGLHKUSA-N ;
	(what is this?) (verify)

Hydromorphinol (RAM-320, 14-hydroxydihydromorphine),^[2] is an opiate analogue that is a derivative of morphine, where the 14-position has been hydroxylated and the 7,8- double bond saturated.^[3] It has similar effects to morphine such as sedation, analgesia and respiratory depression, but is twice as potent as morphine^[2] and has a steeper dose-response curve and longer half-life.^[4] It is used in medicine as the bitartrate salt (free base conversion ratio 0.643, molecular weight 471.5) and hydrochloride (free base conversion ratio 0.770, molecular weight 393.9)

Hydromorphinol has also been discovered to occur naturally in trace amounts within opium, although this is a very rare occurrence.^[5]

It is also called α-oxymorphol, and oxymorphol is itself a mixture of hydromorphinol and 4,5α-epoxy-17-methylmorphinan-3,6β,14-triol (β-oxymorphol) which is different at position 6 on the morphine carbon skeleton.

Hydromorphinol was developed in Austria in 1932. In the United States, it was never available and is classified as a Schedule I drug with a DEA ACSCN of 9301. The salts in use are the bitartrate (free base conversion ratio 0.643) and hydrochloride (0.770). The 2014, national aggregate manufacturing quota was 2 grams, unchanged from prior years.^[6]

Hydromorphinol is metabolized mainly in the liver in the same fashion as many other opioids and is itself a minor active metabolite of 14-hydroxydihydrocodeine, an uncommonly used opiate (but is therefore also an active metabolite of a first-order active metabolite of oxycodone).

It is distributed under the trade name Numorphan in some countries. It is controlled under the Single Convention On Narcotic Drugs.

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.
^ ^a ^b US 2960505, Weiss U, "Morphine derivative", published 11/15/1960
^ Weiss U, Daum SJ (January 1965). "Derivatives of Morphine. IV.114-Hydroxymorphine and 14-Hydroxydihydromorphine". Journal of Medicinal Chemistry. 8: 123–5. doi:10.1021/jm00325a028. PMID 14287245.
^ Plummer JL, Cmielewski PL, Reynolds GD, Gourlay GK, Cherry DA (March 1990). "Influence of polarity on dose-response relationships of intrathecal opioids in rats". Pain. 40 (3): 339–47. doi:10.1016/0304-3959(90)91131-2. PMID 2326098. S2CID 2100412.
^ Ginsburg D (1959). "Some recent advances in the chemistry of the opium alkaloids". UNODC Bulletin on Narcotics (3).
^ "Quotas 2014". DEA Diversion Control Division. Archived from the original on 2016-03-04. Retrieved 2016-02-27.

[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.

[US2960505-2] US 2960505, Weiss U, "Morphine derivative", published 11/15/1960

[3] Weiss U, Daum SJ (January 1965). "Derivatives of Morphine. IV.114-Hydroxymorphine and 14-Hydroxydihydromorphine". Journal of Medicinal Chemistry. 8: 123–5. doi:10.1021/jm00325a028. PMID 14287245.

[4] Plummer JL, Cmielewski PL, Reynolds GD, Gourlay GK, Cherry DA (March 1990). "Influence of polarity on dose-response relationships of intrathecal opioids in rats". Pain. 40 (3): 339–47. doi:10.1016/0304-3959(90)91131-2. PMID 2326098. S2CID 2100412.

[5] Ginsburg D (1959). "Some recent advances in the chemistry of the opium alkaloids". UNODC Bulletin on Narcotics (3).

[6] "Quotas 2014". DEA Diversion Control Division. Archived from the original on 2016-03-04. Retrieved 2016-02-27.

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See also

References