Details of the Drug Combination

General Information of Drug Combination (ID: DCD1HJT)

Drug Combination Name
Ketamine Methadone
Indication
Disease Entry Status REF
Laminectomy Phase 4 [1]
Component Drugs Ketamine   DMT5HA4 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 Ketamine
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [2]
Anxiety N.A. Approved [3]
Bipolar disorder 6A60 Approved [3]
Depression 6A70-6A7Z Approved [3]
Traumatic brain injury NA07.Z Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [4]
Chronic pain MG30 Investigative [3]
Ketamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
N-methyl-D-aspartate receptor (NMDAR) TT9IK2Z NOUNIPROTAC Antagonist [8]
------------------------------------------------------------------------------------
Ketamine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [9]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [9]
------------------------------------------------------------------------------------
Ketamine Interacts with 10 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Zinc finger protein SNAI2 (SNAI2) OT7Y8EJ2 SNAI2_HUMAN Increases Expression [7]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Increases Expression [7]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Expression [10]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Expression [7]
Amyloid-beta precursor protein (APP) OTKFD7R4 A4_HUMAN Increases Expression [11]
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Decreases Expression [7]
Protein S100-A4 (S100A4) OTLRGFSQ S10A4_HUMAN Increases Expression [7]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [12]
Actin, aortic smooth muscle (ACTA2) OTEDLG8E ACTA_HUMAN Increases Expression [7]
Sodium/hydrogen exchanger 6 (SLC9A6) OT5N47TC SL9A6_HUMAN Decreases Expression [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DOT(s)
Indication(s) of Methadone
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [5]
Dry cough MD12 Approved [6]
Pain MG30-MG3Z Approved [5]
Methadone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Agonist [13]
------------------------------------------------------------------------------------
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 [14]
------------------------------------------------------------------------------------
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 [15]
Aromatase (CYP19A1) DEQX145 CP19A_HUMAN Metabolism [16]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [17]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [15]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [15]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [18]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [15]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [15]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [15]
------------------------------------------------------------------------------------
⏷ Show the Full List of 10 DME(s)
Methadone Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [19]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [20]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [21]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [21]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Affects Localization [22]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT02252432) The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 076092.
3 Ketamine FDA Label
4 ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
5 Methadone FDA Label
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
7 Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-1. Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F961-F972. doi: 10.1152/ajprenal.00686.2016. Epub 2017 Mar 22.
8 Ketamine modulates theta and gamma oscillations. J Cogn Neurosci. 2010 Jul;22(7):1452-64.
9 Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos. 2002 Jul;30(7):853-8.
10 Ketamine hypertension and the renin-angiotensin system. Clin Exp Hypertens A. 1983;5(6):875-83. doi: 10.3109/10641968309081814.
11 Ketamine promotes the amyloidogenic pathway by regulating endosomal pH. Toxicology. 2022 Apr 15;471:153163. doi: 10.1016/j.tox.2022.153163. Epub 2022 Apr 1.
12 Lipoxin A4 methyl ester attenuated ketamine-induced neurotoxicity in SH-SY5Y cells via regulating leptin pathway. Toxicol In Vitro. 2023 Jun;89:105581. doi: 10.1016/j.tiv.2023.105581. Epub 2023 Mar 11.
13 Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
14 In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites. Pharmacology. 2007;80(4):304-11.
15 Methadone metabolism and drug-drug interactions: in vitro and in vivo literature review. J Pharm Sci. 2018 Dec;107(12):2983-2991.
16 Bidirectional transfer of methadone across human placenta. Biochem Pharmacol. 2005 Jan 1;69(1):187-97.
17 Methadone--metabolism, pharmacokinetics and interactions. Pharmacol Res. 2004 Dec;50(6):551-9.
18 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.
19 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.
20 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.
21 opioid receptor agonist-selective regulation of interleukin-4 in T lymphocytes. J Neuroimmunol. 2013 Oct 15;263(1-2):35-42. doi: 10.1016/j.jneuroim.2013.07.012. Epub 2013 Jul 25.
22 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.