Details of the Drug Combination

General Information of Drug Combination (ID: DC6OONO)

Drug Combination Name
Spironolactone Dihydralazine
Indication
Disease Entry Status REF
Aortic Stenosis, Severe Phase 3 [1]
Component Drugs Spironolactone   DM2AQ5N Dihydralazine   DMZIXU9
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 Spironolactone
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Congestive heart failure BD10 Approved [3]
Edema MG29 Approved [2]
Hyperaldosteronism 5A72 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Spironolactone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Modulator [6]
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Spironolactone Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [7]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [8]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Expression [8]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [9]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [10]
Myb-related protein A (MYBL1) OTBJMC2P MYBA_HUMAN Increases Expression [11]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [8]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Increases Expression [11]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Response To Substance [12]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Dihydralazine
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [5]
Dihydralazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [13]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [14]
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Metabolism [15]
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Dihydralazine Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [16]
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References

1 ClinicalTrials.gov (NCT05230901) Effect of Antifibrotic Therapy on Regression of Myocardial Fibrosis After Transcatheter Aortic Valve Implantation (TAVI) in Aortic Stenosis Patients With High Fibrotic Burden
2 Spironolactone FDA Label
3 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: 2875).
4 Spironolactone in Covid-19 Induced ARDS
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
8 Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001 Apr;37(5):1228-33. doi: 10.1016/s0735-1097(01)01116-0.
9 Effect of spironolactone on impaired fibrinolysis of hypertensive patients. Kidney Blood Press Res. 2002;25(4):260-4. doi: 10.1159/000066348.
10 Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells. Toxicology. 2011 Jul 11;285(1-2):18-24. doi: 10.1016/j.tox.2011.03.015. Epub 2011 Apr 1.
11 A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
12 Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study. Hypertension. 1980 Sep-Oct;2(5):672-9. doi: 10.1161/01.hyp.2.5.672.
13 Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279-304.
14 Mechanism-based inactivation of cytochrome P450s 1A2 and 3A4 by dihydralazine in human liver microsomes. Chem Res Toxicol. 1999 Oct;12(10):1028-32.
15 The influence of the acetylator phenotype for the clinical use of dihydralazine. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23 Suppl 1:S74-8.
16 Additive effects of dihydralazine during enflurane or isoflurane hypotensive anaesthesia for spinal fusion. Can J Anaesth. 1988 May;35(3 ( Pt 1)):242-8. doi: 10.1007/BF03010617.