General Information of Drug Combination (ID: DCOJJC8)

Drug Combination Name
Fentanyl Isoflurane
Indication
Disease Entry Status REF
Anesthesia; Adverse Effect Phase 1 [1]
Component Drugs Fentanyl   DM8WAHT Isoflurane   DMY6T31
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 Fentanyl
Disease Entry ICD 11 Status REF
Analgesia MB40.8 Approved [2]
Traumatic brain injury NA07.Z Approved [3]
Cancer related pain MG30 Phase 3 [4]
Pain MG30-MG3Z Phase 3 [5]
Chronic pain MG30 Phase 1 [6]
Fentanyl 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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Fentanyl Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Fentanyl Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [11]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [12]
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Fentanyl Interacts with 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [13]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases Phosphorylation [14]
Phospholipase D2 (PLD2) OT86I3WH PLD2_HUMAN Increases Activity [15]
Pro-opiomelanocortin (POMC) OTV41F7T COLI_HUMAN Decreases Expression [16]
Interleukin-4 (IL4) OTOXBWAU IL4_HUMAN Increases Expression [15]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [17]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Increases Phosphorylation [15]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Increases Phosphorylation [15]
Beta-arrestin-2 (ARRB2) OTAEJZCI ARRB2_HUMAN Affects Localization [18]
Interleukin-2 (IL2) OTGI4NSA IL2_HUMAN Decreases Expression [15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [19]
Opioid growth factor receptor (OGFR) OTROS6RJ OGFR_HUMAN Increases ADR [20]
Adenylate cyclase type 1 (ADCY1) OTSLLFZO ADCY1_HUMAN Increases ADR [20]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Isoflurane
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [7]
Isoflurane Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Glutamate receptor AMPA (GRIA) TTAN6JD NOUNIPROTAC Agonist [21]
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Isoflurane Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [22]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [23]
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Isoflurane Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Affects Activity [24]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [25]
Beta-secretase 1 (BACE1) OTCA7B6A BACE1_HUMAN Increases Expression [26]
Nicastrin (NCSTN) OT5QBTA4 NICA_HUMAN Increases Expression [26]
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References

1 ClinicalTrials.gov (NCT03882788) The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 Fentanyl FDA Label
4 ClinicalTrials.gov (NCT00822614) Safety of Fentanyl TAIFUN Treatment. U.S. National Institutes of Health.
5 A Phase III study to assess the clinical utility of low-dose fentanyl transdermal system in patients with chronic nonmalignant pain. Curr Med Res Opin. 2006 Aug;22(8):1493-501.
6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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: 2505).
8 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
9 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
10 Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33.
11 Pharmacogenomics as molecular autopsy for forensic toxicology: genotyping cytochrome P450 3A4*1B and 3A5*3 for 25 fentanyl cases. J Anal Toxicol. 2005 Oct;29(7):590-8.
12 Drug Interactions Flockhart Table
13 P-Glycoprotein on Blood-Brain Barrier Plays a Vital Role in Fentanyl Brain Exposure and Respiratory Toxicity in Rats. Toxicol Sci. 2018 Jul 1;164(1):353-362. doi: 10.1093/toxsci/kfy093.
14 A G protein-biased ligand at the ?-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17.
15 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.
16 Serum beta-endorphin response to stress before and after operation under fentanyl anesthesia in neonates, infants and preschool children. Eur J Pediatr Surg. 2010 Mar;20(2):106-10. doi: 10.1055/s-0029-1243620. Epub 2010 Jan 18.
17 Mechanisms of the inhibition of nuclear factor-B by morphine in neuronal cells. Mol Pharmacol. 2012 Apr;81(4):587-97. doi: 10.1124/mol.111.076620. Epub 2012 Jan 18.
18 Functional and structural characterization of axonal opioid receptors as targets for analgesia. Mol Pain. 2016 Mar 1;12:1744806916628734. doi: 10.1177/1744806916628734. Print 2016.
19 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
20 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
21 Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit. Brain Res. 2005 Jan 25;1032(1-2):30-5.
22 Clinical isoflurane metabolism by cytochrome P450 2E1. Anesthesiology. 1999 Mar;90(3):766-71.
23 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
24 The stress response to induced hypotension for cerebral aneurysm surgery: a comparison of two hypotensive techniques. Can J Anaesth. 1988 Mar;35(2):111-5. doi: 10.1007/BF03010648.
25 Sevoflurane-mediated activation of p38-mitogen-activated stresskinase is independent of apoptosis in Jurkat T-cells. Anesth Analg. 2008 Apr;106(4):1150-60, table of contents. doi: 10.1213/ane.0b013e3181683d37.
26 The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation. J Neurosci. 2007 Feb 7;27(6):1247-54. doi: 10.1523/JNEUROSCI.5320-06.2007.