Details of the Drug Combination

General Information of Drug Combination (ID: DCH4EHW)

Drug Combination Name
Duloxetine Pregabalin
Indication
Disease Entry Status REF
Central Sensitisation Phase 1 [1]
Component Drugs Duloxetine   DM9BI7M Pregabalin   DMDVP3B
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 Duloxetine
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [2]
Major depressive disorder 6A70.3 Approved [3]
Stress urinary incontinence MF50.20 Approved [3]
Traumatic brain injury NA07.Z Approved [3]
Duloxetine Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [6]
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Inhibitor [6]
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Duloxetine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [7]
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Duloxetine Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [8]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [9]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [10]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [12]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Affects Localization [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [10]
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⏷ Show the Full List of 7 DOT(s)
Indication(s) of Pregabalin
Disease Entry ICD 11 Status REF
Chronic obstructive pulmonary disease CA22 Approved [4]
Epilepsy 8A60-8A68 Approved [5]
Pain MG30-MG3Z Approved [5]
Postherpetic neuralgia 1E91.5 Approved [5]
Vulvodynia N.A. Approved [5]
Chronic pain MG30 Investigative [5]
Neuralgia N.A. Investigative [5]
Pregabalin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1) TTFK1JQ CA2D1_HUMAN Modulator [13]
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Pregabalin Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
L-type amino acid transporter 1 (SLC7A5) DT48T0N LAT1_HUMAN Substrate [14]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Fibromyalgia DCB5CMJ N. A. Phase 1 [15]
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References

1 ClinicalTrials.gov (NCT05020600) The Effect of Central Sensitization on Treatment Response in Patients With Fibromyalgia
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: 202).
3 Duloxetine FDA Label
4 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: 5484).
5 Pregabalin FDA Label
6 Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
7 Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94.
8 Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay. Toxicol In Vitro. 2018 Mar;47:63-71.
9 Hyperprolactinemia and galactorrhea induced by serotonin and norepinephrine reuptake inhibiting antidepressants. Am J Psychiatry. 2007 Jul;164(7):1121-2. doi: 10.1176/ajp.2007.164.7.1121a.
10 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
11 Duloxetine Protects Human Neuroblastoma Cells from Oxidative Stress-Induced Cell Death Through Akt/Nrf-2/HO-1 Pathway. Neurochem Res. 2018 Feb;43(2):387-396. doi: 10.1007/s11064-017-2433-3. Epub 2017 Nov 13.
12 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.
13 Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons. Mol Pharmacol. 2006 Aug;70(2):467-76.
14 Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharm Res. 2018 Oct 29;35(12):246.
15 ClinicalTrials.gov (NCT01268631) Mechanism-based Choice of Therapy: Can Treatments Success in Fibromyalgia Patients be Coupled to Psychophysical Pain Modulation Profile?