Details of the Drug Combination

General Information of Drug Combination (ID: DCCHNDO)

Drug Combination Name
Pilocarpine Phentolamine
Indication
Disease Entry Status REF
Presbyopia Phase 2 [1]
Component Drugs Pilocarpine   DMV9ADG Phentolamine   DMXYJOB
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 Pilocarpine
Disease Entry ICD 11 Status REF
Glaucoma/ocular hypertension 9C61 Approved [2]
Ocular hypertension 9C61.01 Approved [3]
Pilocarpine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Muscarinic acetylcholine receptor M5 (CHRM5) TTH18TF ACM5_HUMAN Agonist [6]
------------------------------------------------------------------------------------
Pilocarpine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [8]
------------------------------------------------------------------------------------
Pilocarpine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Delta-type opioid receptor (OPRD1) OT164PA1 OPRD_HUMAN Increases ADR [9]
Mu-type opioid receptor (OPRM1) OT16AAT8 OPRM_HUMAN Increases ADR [9]
------------------------------------------------------------------------------------
Indication(s) of Phentolamine
Disease Entry ICD 11 Status REF
Brain ischaemia 8B1Z Approved [4]
Dermal necrosis MC85 Approved [5]
Hypertensive emergency BA03 Approved [4]
Pheochromocytoma 5A75 Approved [4]
Peripheral vascular disease BD4Z Investigative [4]
Phentolamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [10]
------------------------------------------------------------------------------------
Phentolamine Interacts with 14 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Decreases Expression [11]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [12]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Decreases Expression [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [11]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [13]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Affects Binding [14]
Alpha-1A adrenergic receptor (ADRA1A) OTUIWCL5 ADA1A_HUMAN Affects Binding [14]
Alpha-1B adrenergic receptor (ADRA1B) OTSAYAFD ADA1B_HUMAN Affects Binding [14]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [15]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [16]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Decreases Expression [11]
Sulfotransferase 1A1 (SULT1A1) OT0K7JIE ST1A1_HUMAN Increases Sulfation [17]
Sulfotransferase 1A3 (SULT1A4) OTHJ8WWV ST1A3_HUMAN Increases Sulfation [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 DOT(s)

References

1 ClinicalTrials.gov (NCT04675151) Safety and Efficacy of Nyxol With Pilocarpine Eye Drops in Subjects With Presbyopia
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: 305).
3 Pilocarpine FDA Label
4 Phentolamine FDA Label
5 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: 502).
6 Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6.
7 The inhibition of CYP enzymes in mouse and human liver by pilocarpine. Br J Pharmacol. 1995 Feb;114(4):832-6.
8 Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine. FEBS J. 2012 May;279(9):1621-31.
9 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.
10 Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R330-6.
11 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
12 Mediation of renin release in essential hypertension by alpha-adrenoreceptors. J Cardiovasc Pharmacol. 1981 Nov-Dec;3(6):1153-61. doi: 10.1097/00005344-198111000-00001.
13 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
14 Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
15 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
16 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
17 Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms. Drug Metab Dispos. 2001 Mar;29(3):274-81.