Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM65AGJ)

• Drug Name: Oxymorphone Drug Info
• Synonyms: Oxymorphone (abuse-resistant, pain); Oxymorphone (abuse-resistant, pain), Pain Therapeutics/ King Pharmaceuticals; Oxymorphone (abuse-resistant, pain), Pain Therapeutics/Pfizer

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Approved	[1]
Chronic pain	MG30	Investigative	[2]

• Therapeutic Class: Neurology Agents
• Cross-matching ID:
  PubChem CID: 5284604
  ChEBI ID: CHEBI:7865
  CAS Number: CAS 76-41-5
  TTD Drug ID: DM65AGJ
  INTEDE Drug ID: DR1226
  ACDINA Drug ID: D00503

Molecule-Related Drug Atlas

Drug(s) Targeting Opioid receptor (OPR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methadone	DMTW6IU	Advanced cancer	2A00-2F9Z	Approved	[5]
Ketobemidone	DMM3L6Z	Pain	MG30-MG3Z	Approved	[6]
Dextropropoxyphene	DM23HCX	Pain	MG30-MG3Z	Approved	[7]
Sufentanil	DMU7YEL	Analgesia	MB40.8	Approved	[8]
Naltrexone	DMUL45H	Alcohol dependence	6C40.2	Approved	[9]
Levorphanol	DMGS80V	Pain	MG30-MG3Z	Approved	[10]
Pentazocine	DM1XBHS	Pain	MG30-MG3Z	Approved	[11]
Nalmefene	DM4YWCZ	Opioid dependence	6C43.2Z	Approved	[12]
Tilidine	DMJW0VS	Pain	MG30-MG3Z	Approved	[13]
Dihydrocodeine	DMB0FWL	Allergic rhinitis	CA08.0	Phase 4	[14]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[27]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[28]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[29]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[30]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Modulator	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Oxymorphone FDA Label
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7094).
• [4] Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. Br J Clin Pharmacol. 2010 Jul;70(1):78-87.
• [5] Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
• [6] The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3-dimethylamino-1,1-diphenylbutene. Pharmacol Toxicol. 1996 Aug;79(2):103-4.
• [7] Retrospective diagnosis of an adverse drug reaction in a breastfed neonate: liquid chromatography-tandem mass spectrometry quantification of dextropropoxyphene and norpropoxyphene in newborn and maternal hair. J Anal Toxicol. 2008 Nov-Dec;39(9):787-9.
• [8] mu-opioid receptor-stimulated synthesis of reactive oxygen species is mediated via phospholipase D2. J Neurochem. 2009 Aug;110(4):1288-96.
• [9] An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
• [10] Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. J Pharmacol Exp Ther. 2004 May;309(2):515-22.
• [11] Functional characterization of a sigma receptor and its gene expression by haloperidol. Nippon Yakurigaku Zasshi. 1999 Jul;114(1):61-8.
• [12] Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospin... J Pharmacol Exp Ther. 2009 Feb;328(2):588-97.
• [13] Actions of tilidine and nortilidine on cloned opioid receptors. Eur J Pharmacol. 2005 Jan 4;506(3):205-8.
• [14] Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63.
• [15] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [20] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [23] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [24] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [25] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [26] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [27] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [28] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [29] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [30] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [31] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.