General Information of Drug Combination (ID: DC8IXD7)

Drug Combination Name
Proparacaine Ropivacaine
Indication
Disease Entry Status REF
Cataract Unilateral Pending Extraction Phase 1 [1]
Component Drugs Proparacaine   DMLS39E Ropivacaine   DMSPJG2
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 Proparacaine
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [2]
Proparacaine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.8 (SCN10A) TT90XZ8 SCNAA_HUMAN Modulator [5]
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Indication(s) of Ropivacaine
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [3]
Appendicitis DB10 Approved [4]
Ropivacaine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.8 (SCN10A) TT90XZ8 SCNAA_HUMAN Modulator [5]
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Ropivacaine Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [9]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [9]
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Ropivacaine Interacts with 24 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1) OTKPWB7Q AIFM1_HUMAN Increases Expression [10]
L-lactate dehydrogenase A chain (LDHA) OTN7K4XB LDHA_HUMAN Increases Expression [11]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases Expression [11]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [11]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [12]
Caspase-1 (CASP1) OTZ3YQFU CASP1_HUMAN Increases Cleavage [11]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [6]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [13]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [6]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Decreases Activity [14]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Decreases Expression [13]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Increases Cleavage [11]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [6]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [6]
Interleukin-18 (IL18) OTBB2A8O IL18_HUMAN Increases Expression [11]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [6]
NACHT, LRR and PYD domains-containing protein 3 (NLRP3) OTZM6MHU NLRP3_HUMAN Increases Expression [11]
Sulfotransferase 1A1 (SULT1A1) OT0K7JIE ST1A1_HUMAN Increases Sulfation [15]
Histamine H1 receptor (HRH1) OT8F9FV6 HRH1_HUMAN Affects Binding [16]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Response To Substance [12]
Sulfotransferase 1E1 (SULT1E1) OTGPJ517 ST1E1_HUMAN Increases Sulfation [15]
Sulfotransferase 1A3 (SULT1A4) OTHJ8WWV ST1A3_HUMAN Increases Sulfation [15]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Decreases Response To Substance [12]
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⏷ Show the Full List of 24 DOT(s)

References

1 ClinicalTrials.gov (NCT02925832) Comparing Ropivacaine and Bupivacaine in DTFNB Anesthesia in Patients Undergoing Phacoemulsification
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: 7283).
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: 7602).
4 Ropivacaine FDA Label
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6 Ropivacaine inhibits proliferation?and invasion?and promotes apoptosis and autophagy in bladder cancer cells via inhibiting PI3K/AKT pathway. J Biochem Mol Toxicol. 2023 Jan;37(1):e23233. doi: 10.1002/jbt.23233. Epub 2022 Oct 3.
7 Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450. Anesthesiology. 1995 Jan;82(1):214-20.
8 Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther. 1998 Nov;64(5):484-91.
9 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10 Effect of parthanatos on ropivacaine-induced damage in SH-SY5Y cells. Clin Exp Pharmacol Physiol. 2017 May;44(5):586-594. doi: 10.1111/1440-1681.12730.
11 Dexmedetomidine protects against Ropivacaine-induced neuronal pyroptosis via the Nrf2/HO-1 pathway. J Toxicol Sci. 2023;48(3):139-148. doi: 10.2131/jts.48.139.
12 Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine. Cell Res. 2004 Oct;14(5):415-22. doi: 10.1038/sj.cr.7290242.
13 Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine. J Bone Joint Surg Am. 2010 Mar;92(3):609-18. doi: 10.2106/JBJS.H.01847.
14 Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current. Anesthesiology. 2006 Sep;105(3):511-20. doi: 10.1097/00000542-200609000-00015.
15 Studies on sulfation of synthesized metabolites from the local anesthetics ropivacaine and lidocaine using human cloned sulfotransferases. Drug Metab Dispos. 1999 Sep;27(9):1057-63.
16 H(1)R mediates local anesthetic-induced vascular permeability in angioedema. Toxicol Appl Pharmacol. 2020 Apr 1;392:114921. doi: 10.1016/j.taap.2020.114921. Epub 2020 Feb 12.