General Information of Drug Combination (ID: DCGMJ03)

Drug Combination Name
Naloxone Oxycodone
Indication
Disease Entry Status REF
Postoperative Pain Phase 1 [1]
Component Drugs Naloxone   DM3FXMA Oxycodone   DMXLKHV
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Naloxone
Disease Entry ICD 11 Status REF
Narcotic depression 6A7Z Approved [2]
Pain MG30-MG3Z Approved [3]
Pruritus EC90 Phase 3 [4]
Respiratory depression MD11.5 Phase 3 [5]
Opioid dependence 6C43.2Z Phase 1 [5]
Naloxone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor mu (MOP) TTKWM86 OPRM_HUMAN Antagonist [10]
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Naloxone Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [11]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [12]
Vasopressin-neurophysin 2-copeptin (AVP) OTAVZ76K NEU2_HUMAN Decreases Secretion [13]
Pro-opiomelanocortin (POMC) OTV41F7T COLI_HUMAN Increases Expression [14]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [15]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Affects Expression [16]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Response To Substance [17]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [18]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Affects Binding [19]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Response To Substance [20]
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⏷ Show the Full List of 10 DOT(s)
Indication(s) of Oxycodone
Disease Entry ICD 11 Status REF
Osteoarthritis FA00-FA05 Approved [6]
Pain MG30-MG3Z Approved [7]
Back pain ME84.Z Phase 3 [8]
Oxycodone Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor mu (MOP) TTKWM86 OPRM_HUMAN Modulator [21]
Opioid receptor delta (OPRD1) TT27RFC OPRD_HUMAN Agonist [22]
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Oxycodone Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1) OTM0GDTP IF2A_HUMAN Increases Phosphorylation [18]
Endoplasmic reticulum chaperone BiP (HSPA5) OTFUIRAO BIP_HUMAN Increases Expression [18]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Increases Expression [18]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Affects Metabolism [23]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Response To Substance [24]
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References

1 ClinicalTrials.gov (NCT01109511) A Comparison of Oxycodone/Naloxone and Oxycodone After Laparoscopic Hysterectomy
2 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: 1668).
3 Naloxone FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Oxycodone FDA Label
7 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: 7093).
8 ClinicalTrials.gov (NCT01427283) A Study of Oxycodone/Naloxone Controlled-release Tablets (OXN) to Assess Analgesic Efficacy and Management of Opioid-induced Constipation (OIC) in Opioid-experienced Subjects With Moderate to Severe Chronic Low Back Pain. U.S. National Institutes of Health.
9 Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.
10 OxyContin abuse and overdose. Postgrad Med. 2009 Mar;121(2):163-7.
11 beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
12 Opioid peptides attenuate blood pressure increase in acute respiratory failure. Peptides. 2001 Apr;22(4):631-7. doi: 10.1016/s0196-9781(01)00373-4.
13 Blood pressure and vasopressin in progressive autonomic failure. Response to postural stimulation, L-dopa and naloxone. Brain. 1983 Jun;106 (Pt 2):503-11. doi: 10.1093/brain/106.2.503.
14 Endogenous opioids modulate the cardiovascular response to mental stress. Psychoneuroendocrinology. 1990;15(3):185-92. doi: 10.1016/0306-4530(90)90029-9.
15 Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
16 Influence of naloxone on muscle sympathetic nerve activity, systemic and calf haemodynamics and ambulatory blood pressure after exercise in mild essential hypertension. J Hypertens. 1995 Apr;13(4):447-61.
17 Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009 May 20;29(20):6449-60. doi: 10.1523/JNEUROSCI.0708-09.2009.
18 Chronic oxycodone induces integrated stress response in rat brain. BMC Neurosci. 2015 Sep 16;16:58. doi: 10.1186/s12868-015-0197-8.
19 Human carboxylesterase 1: from drug metabolism to drug discovery. Biochem Soc Trans. 2003 Jun;31(Pt 3):620-4. doi: 10.1042/bst0310620.
20 Interleukin-2-induced antinociception in morphine-insensitive rats. Acta Pharmacol Sin. 2002 Nov;23(11):981-4.
21 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. (Target id: 319).
22 Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
23 Evaluation of Recombinant CYP3A4 Variants on the Metabolism of Oxycodone In Vitro. Chem Res Toxicol. 2021 Jan 18;34(1):103-109. doi: 10.1021/acs.chemrestox.0c00361. Epub 2021 Jan 4.
24 Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol. 2010 Jun;160(4):919-30. doi: 10.1111/j.1476-5381.2010.00709.x.