Details of the Drug Combination

General Information of Drug Combination (ID: DCVBR2M)

Drug Combination Name
Lidocaine Propofol
Indication
Disease Entry Status REF
Pain Phase 1 [1]
Component Drugs Lidocaine   DML4ZOT Propofol   DMB4OLE
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 Lidocaine
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [2]
Carpal tunnel syndrome N.A. Approved [3]
Interstitial cystitis GC00.3 Approved [3]
Long QT syndrome BC65.0 Approved [3]
Pain MG30-MG3Z Approved [3]
Pediculus capitis infestation 1G00.0 Approved [3]
Periodontitis DA0C Approved [3]
Postherpetic neuralgia 1E91.5 Approved [3]
Pthirus pubis infestation N.A. Approved [3]
Dysmenorrhea GA34.3 Phase 2 [4]
Chronic pain MG30 Investigative [3]
Neuralgia N.A. Investigative [3]
Premature ejaculation HA03.0Z Investigative [3]
Pruritus EC90 Investigative [3]
Lidocaine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A) TTN9VTF SCNBA_HUMAN Blocker [9]
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Lidocaine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
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Lidocaine Interacts with 10 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [12]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [14]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [15]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [15]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [13]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [13]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [16]
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⏷ Show the Full List of 10 DME(s)
Lidocaine Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Alpha-1-acid glycoprotein 1 (ORM1) OTZKSBRE A1AG1_HUMAN Affects Binding [17]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Increases ADR [18]
Alkaline phosphatase, placental type (ALPP) OTZU4G9W PPB1_HUMAN Increases ADR [18]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [19]
Neurofilament medium polypeptide (NEFM) OT8VCBNF NFM_HUMAN Decreases Expression [8]
Alpha-1-acid glycoprotein 2 (ORM2) OTRJGZP8 A1AG2_HUMAN Affects Binding [17]
Neuronatin (NNAT) OTNRLO7G NNAT_HUMAN Decreases Expression [8]
Transient receptor potential cation channel subfamily V member 1 (TRPV1) OTHHDR03 TRPV1_HUMAN Increases Activity [20]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Affects Response To Substance [21]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Propofol
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [5]
Leukemia N.A. Approved [6]
Traumatic brain injury NA07.Z Approved [6]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [7]
Propofol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Fatty acid amide hydrolase (FAAH) TTDP1UC NOUNIPROTAC Inhibitor [24]
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Propofol Interacts with 14 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [25]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [26]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [27]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [28]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [29]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [26]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [28]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [28]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [25]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [30]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [28]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [31]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DESD26P UD16_HUMAN Metabolism [32]
Oleamide hydrolase 1 (FAAH) DEUM1EX FAAH1_HUMAN Metabolism [33]
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⏷ Show the Full List of 14 DME(s)
Propofol Interacts with 26 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Leucine-rich colipase-like protein 1 (LRCOL1) OTDXBZF8 LRCL1_HUMAN Decreases Expression [23]
Glutamate dehydrogenase 1, mitochondrial (GLUD1) OTXKOCUH DHE3_HUMAN Decreases Expression [34]
Progonadoliberin-1 (GNRH1) OTH8A44K GON1_HUMAN Increases Expression [35]
Interleukin-2 receptor subunit alpha (IL2RA) OT0MWCHG IL2RA_HUMAN Decreases Secretion [36]
Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) OTTLGRGH GNAI2_HUMAN Decreases Expression [23]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [35]
Small ribosomal subunit protein uS2 (RPSA) OTJZHEGT RSSA_HUMAN Increases Expression [35]
Matrilysin (MMP7) OTVT3SEJ MMP7_HUMAN Increases Expression [35]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Expression [34]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases Expression [35]
Metalloproteinase inhibitor 2 (TIMP2) OT8S1RRP TIMP2_HUMAN Increases Expression [35]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [34]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [34]
Macrosialin (CD68) OTOYEY3J CD68_HUMAN Increases Expression [35]
Carbonic anhydrase 5A, mitochondrial (CA5A) OTP9M7VW CAH5A_HUMAN Decreases Expression [23]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [23]
Protein SET (SET) OTGYYQJO SET_HUMAN Decreases Expression [35]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Increases Expression [35]
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5) OTU4DD4G MGT5A_HUMAN Increases Expression [35]
Mothers against decapentaplegic homolog 2 (SMAD2) OTC6VB4K SMAD2_HUMAN Decreases Expression [35]
Transmembrane channel-like protein 6 (TMC6) OTKH50J4 TMC6_HUMAN Increases Expression [23]
Polycystin-1-like protein 3 (PKD1L3) OTQMYNOW PK1L3_HUMAN Decreases Expression [23]
Uncharacterized protein C10orf67, mitochondrial (C10ORF67) OTX24W0H CJ067_HUMAN Increases Expression [23]
Pinin (PNN) OT0HXICH PININ_HUMAN Decreases Expression [35]
Protein turtle homolog B (IGSF9B) OTNOMYYQ TUTLB_HUMAN Decreases Expression [23]
Mitochondrial pyruvate carrier 1 (MPC1) OT6DYFUO MPC1_HUMAN Decreases Expression [34]
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⏷ Show the Full List of 26 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Topical Anesthesia DCG57SD N. A. Phase 4 [37]
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References

1 ClinicalTrials.gov (NCT02512783) Decreasing Propofol Injection Pain by Pre-Treatment With Lidocaine in Pediatric Procedural Sedation
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: 2623).
3 Lidocaine FDA Label
4 ClinicalTrials.gov (NCT00651313) Efficacy and Safety Study of Lidocaine Vaginal Gel for Recurrent Dysmenorrhea (Painful Periods). U.S. National Institutes of Health.
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: 5464).
6 Propofol FDA Label
7 Propofol and sedation in patients with coronavirus disease. Am J Emerg Med. 2020 Jun 18;S0735-6757(20)30512-X.
8 Lidocaine prevents breast cancer growth by targeting neuronatin to inhibit nerve fibers formation. J Toxicol Sci. 2021;46(7):329-339. doi: 10.2131/jts.46.329.
9 Mechanisms of analgesia of intravenous lidocaine. Rev Bras Anestesiol. 2008 May-Jun;58(3):280-6.
10 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.
11 Pharmacokinetics of lidocaine hydrochloride metabolized by CYP3A4 in Chinese Han volunteers living at low altitude and in native Han and Tibetan Chinese volunteers living at high altitude. Pharmacology. 2016;97(3-4):107-13.
12 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
13 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
14 Involvement of CYP1A2 and CYP3A4 in lidocaine N-deethylation and 3-hydroxylation in humans. Drug Metab Dispos. 2000 Aug;28(8):959-65.
15 Drug Interactions Flockhart Table
16 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
17 Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. doi: 10.1097/00008571-199610000-00004.
18 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.
19 Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
20 The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons. J Clin Invest. 2008 Feb;118(2):763-76. doi: 10.1172/JCI32751.
21 Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel. Circ Res. 2008 Aug 15;103(4):396-404. doi: 10.1161/CIRCRESAHA.108.172619. Epub 2008 Jul 3.
22 Effects of beta-estradiol and propofol on the 4-methylumbelliferone glucuronidation in recombinant human UGT isozymes 1A1, 1A8 and 1A9. Biopharm Drug Dispos. 2004 Nov;25(8):339-44.
23 Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211065972. doi: 10.1177/09603271211065972.
24 Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
25 Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology. 2001 Jan;94(1):110-9.
26 Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
27 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
28 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
29 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
30 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
31 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
32 Pharmacokinetics of propofol and extrahepatic UGT1A6 gene expression in anhepatic rats. Pharmacology. 2009;84(4):219-26.
33 Update of TTD: therapeutic target database. Nucleic Acids Res. 2010 Jan;38(Database issue):D787-91.
34 Sevoflurane but not propofol enhances ovarian cancer cell biology through regulating cellular metabolic and signaling mechanisms. Cell Biol Toxicol. 2023 Aug;39(4):1395-1411. doi: 10.1007/s10565-022-09766-6. Epub 2022 Oct 8.
35 The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence. Cell Biol Toxicol. 2023 Aug;39(4):1561-1575. doi: 10.1007/s10565-022-09747-9. Epub 2022 Aug 12.
36 Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. doi: 10.1017/s0265021505001031.
37 ClinicalTrials.gov (NCT02507440) Impact of Topical Pharyngeal Anesthetics on Discharge of the Patients When Used in Conjunction With Propofol Sedation in Routine EGD's