Oxymorphazone

Oxymorphazone

Systematic (IUPAC) name
(5α,6E)-3,14-dihydroxy-17-methyl-4,5-epoxy-morphinan-6-one hydrazone
Clinical data
Dependence liability	Physical: Guaranteed Psychological: Very High
Addiction liability	Very High
Identifiers
CAS Number	73697-35-5
ATC code	none
PubChem	CID 9577748
ChemSpider	23231158
Synonyms	Oxymorphone hydrazone
Chemical data
Formula	C17H21N3O3
Molar mass	315.367 g/mol
SMILES CN1CC[C@]23[C@@H]4/C(=N/N)/CC[C@]2([C@H]1CC5=C3C(=C(C=C5)O)O4)O
InChI InChI=1S/C17H21N3O3/c1-20-7-6-16-13-9-2-3-11(21)14(13)23-15(16)10(19-18)4-5-17(16,22)12(20)8-9/h2-3,12,15,21-22H,4-8,18H2,1H3/b19-10-/t12-,15+,16+,17-/m1/s1 Key:VOFTYIFRRWVMOO-YKKXUTDFSA-N
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Oxymorphazone is an opioid analgesic drug related to oxymorphone. Oxymorphazone is a potent and long acting μ-opioid agonist which binds irreversibly to the receptor, forming a covalent bond which prevents it from detaching once bound.^[1][2] This gives it an unusual pharmacological profile, and while oxymorphazone is only around half the potency of oxymorphone, with higher doses the analgesic effect becomes extremely long lasting, with a duration of up to 48 hours.^[3] However, tolerance to analgesia develops rapidly with repeated doses,^[4][5][6] as chronically activated opioid receptors are rapidly internalised by β-arrestins, similar to the results of non-covalent binding by repeated doses of agonists with extremely high binding affinity such as lofentanil.^[7][8]

See also

• Chlornaltrexamine, an irreversible mixed μ-opioid agonist-antagonist
• Chloroxymorphamine, another irreversible μ-opioid full agonist
• Naloxazone, an irreversible μ-opioid antagonist

References

1. Galetta S, Ling GS, Wolfin L, Pasternak GW. Receptor binding and analgesic properties of oxymorphazone. Life Sciences. 1982 Sep 20-27;31(12-13):1389-92. PMID 6183551
2. Hahn EF, Carroll-Buatti M, Pasternak GW. Irreversible opiate agonists and antagonists: the 14-hydroxydihydromorphinone azines. Journal of Neuroscience. 1982 May;2(5):572-6. PMID 6176696
3. France CP, Jacobson AE, Woods JH. Discriminative stimulus effects of reversible and irreversible opiate agonists: morphine, oxymorphazone and buprenorphine. Journal of Pharmacology and Experimental Therapeutics. 1984 Sep;230(3):652-7. PMID 6206224
4. Ling GS, Galetta S, Pasternak GW. Oxymorphazone: a long-acting opiate analgesic. Cellular and Molecular Neurobiology. 1984 Mar;4(1):1-13. PMID 6204757
5. Williams CL, Bodnar RJ, Clark JE, Hahn EF, Burks TF, Pasternak GW. Irreversible opiate agonists and antagonists. IV. Analgesic actions of 14-hydroxydihydromorphinone hydrazones. Journal of Pharmacology and Experimental Therapeutics. 1988 Apr;245(1):8-12. PMID 2452249
6. Benyhe S, Hoffmann G, Varga E, Hosztafi S, Toth G, Borsodi A, Wollemann M. Effects of oxymorphazone in frogs: long lasting antinociception in vivo, and apparently irreversible binding in vitro. Life Sciences. 1989;44(24):1847-57. PMID 2472540
7. Marie N, Aguila B, Allouche S. Tracking the opioid receptors on the way of desensitization. Cellular Signalling. 2006 Nov;18(11):1815-33. doi:10.1016/j.cellsig.2006.03.015 PMID 16750901
8. DuPen A, Shen D, Ersek M. Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Management Nursing. 2007 Sep;8(3):113-21. doi:10.1016/j.pmn.2007.02.004 PMID 17723928