Details of the Drug Combination

General Information of Drug Combination (ID: DCGMJ03)

• Drug Combination Name: Naloxone + Oxycodone
• Indication: Postoperative Pain; Status: Phase 1 [1]
• Component Drugs:
  Naloxone (DM3FXMA): Small molecular drug
  Oxycodone (DMXLKHV): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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]

Naloxone Interacts with 5 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]

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	[16]
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Agonist	[17]

Oxycodone Interacts with 2 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]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[18]

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] 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).
• [17] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [18] Chronic oxycodone induces integrated stress response in rat brain. BMC Neurosci. 2015 Sep 16;16:58. doi: 10.1186/s12868-015-0197-8.