Details of the Drug Combination

General Information of Drug Combination (ID: DCX6HRV)

Drug Combination Name
Morphine Methadone
Indication
Disease Entry Status REF
Cancer Phase 1 [1]
Component Drugs Morphine   DMRMS0L Methadone   DMTW6IU
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 Morphine
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [2]
Chronic pain MG30 Approved [3]
Pain MG30-MG3Z Approved [2]
Diarrhea ME05.1 Investigative [2]
Morphine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor mu (MOP) TTKWM86 OPRM_HUMAN Modulator [8]
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Morphine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [10]
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Morphine Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [15]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [16]
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⏷ Show the Full List of 6 DME(s)
Morphine Interacts with 47 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Chemical Synthesis [17]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response [18]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases Response [18]
Toll-like receptor 4 (TLR4) OTP7ML3S TLR4_HUMAN Affects Binding [19]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [20]
LIM homeobox transcription factor 1-beta (LMX1B) OTM8145D LMX1B_HUMAN Increases Expression [21]
Krueppel-like factor 7 (KLF7) OTS3YVA0 KLF7_HUMAN Increases Expression [22]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [23]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Increases Expression [24]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Expression [24]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [25]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [21]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [26]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Secretion [25]
Coagulation factor VII (F7) OTGNJ97M FA7_HUMAN Increases Expression [24]
Fibroblast growth factor 2 (FGF2) OT7YUJ9F FGF2_HUMAN Decreases Secretion [25]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [27]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [28]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [23]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [26]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [26]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Expression [29]
Kappa-type opioid receptor (OPRK1) OTXCZF4L OPRK_HUMAN Increases Activity [30]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [27]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [20]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [26]
Eukaryotic translation initiation factor 5A-1 (EIF5A) OTQ8DJX5 IF5A1_HUMAN Increases Expression [21]
C-C motif chemokine 8 (CCL8) OTCTWYN8 CCL8_HUMAN Increases Secretion [25]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Increases Secretion [20]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Phosphorylation [23]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [27]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [31]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Decreases Expression [29]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [32]
DNA damage-binding protein 2 (DDB2) OTO8HVVB DDB2_HUMAN Increases Expression [21]
Ninjurin-1 (NINJ1) OTLRZ1EU NINJ1_HUMAN Increases Expression [21]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Increases Expression [21]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Increases Chemical Synthesis [33]
Interleukin-1 receptor antagonist protein (IL1RN) OT308CBE IL1RA_HUMAN Affects Response To Substance [34]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Increases ADR [35]
Beta-arrestin-2 (ARRB2) OTAEJZCI ARRB2_HUMAN Affects Response To Substance [36]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Chemical Synthesis [37]
Signal transducer and activator of transcription 6 (STAT6) OTCKMP49 STAT6_HUMAN Affects Response To Substance [36]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases ADR [35]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases ADR [35]
Platelet-derived growth factor subunit B (PDGFB) OTMFMFC3 PDGFB_HUMAN Decreases Response To Substance [38]
Cholinesterase (BCHE) OTOH3WQ9 CHLE_HUMAN Increases Chemical Synthesis [33]
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⏷ Show the Full List of 47 DOT(s)
Indication(s) of Methadone
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [4]
Dry cough MD12 Approved [3]
Pain MG30-MG3Z Approved [4]
Methadone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Agonist [39]
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Methadone Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [40]
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Methadone Interacts with 10 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [41]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [42]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [43]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [41]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [41]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [44]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [41]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [41]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [41]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [41]
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⏷ Show the Full List of 10 DME(s)
Methadone Interacts with 16 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [45]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [46]
Toll-like receptor 4 (TLR4) OTP7ML3S TLR4_HUMAN Affects Binding [19]
Phospholipase D2 (PLD2) OT86I3WH PLD2_HUMAN Increases Activity [26]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [47]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Response To Substance [48]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [26]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [49]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [23]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [26]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [26]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases Expression [50]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [26]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [51]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Affects Localization [51]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [52]
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⏷ Show the Full List of 16 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Pain DCN4K8R N. A. Phase 1 [53]
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References

1 ClinicalTrials.gov (NCT03324815) Methadone Associated With Morphine for Cancer Pain
2 Morphine FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Methadone FDA Label
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6 Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human udp-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7. Drug Metab Dispos. 2003 Sep;31(9):1086-9. doi: 10.1124/dmd.31.9.1086.
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37 Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases. J Pharmacol Exp Ther. 1996 Nov;279(2):713-7.
38 A growth factor attenuates HIV-1 Tat and morphine induced damage to human neurons: implication in HIV/AIDS-drug abuse cases. PLoS One. 2011 Mar 24;6(3):e18116. doi: 10.1371/journal.pone.0018116.
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40 In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites. Pharmacology. 2007;80(4):304-11.
41 Methadone metabolism and drug-drug interactions: in vitro and in vivo literature review. J Pharm Sci. 2018 Dec;107(12):2983-2991.
42 Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
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44 Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol. 1996 Mar;9(2):365-73.
45 Expression, purification, and characterization of mouse CYP2d22. Drug Metab Dispos. 2006 Jul;34(7):1167-74.
46 Comparative effects of drugs on P-glycoprotein expression and activity using rat and human trophoblast models. Toxicol In Vitro. 2010 Mar;24(2):630-7. doi: 10.1016/j.tiv.2009.10.005. Epub 2009 Oct 17.
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48 Psychoneuroendocrine effects of methadone maintenance. Psychoneuroendocrinology. 1989;14(5):371-91. doi: 10.1016/0306-4530(89)90007-3.
49 Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
50 Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment. Physiol Res. 2005;54(1):73-78. doi: 10.33549/physiolres.930568.
51 Methadone induces necrotic-like cell death in SH-SY5Y cells by an impairment of mitochondrial ATP synthesis. Biochim Biophys Acta. 2010 Nov;1802(11):1036-47. doi: 10.1016/j.bbadis.2010.07.024. Epub 2010 Aug 3.
52 QTc interval prolongation associated with intravenous methadone. Pain. 2003 Oct;105(3):499-506. doi: 10.1016/S0304-3959(03)00205-7.
53 ClinicalTrials.gov (NCT00558870) Role of Methadone As Co-Opioid Analgesic