Details of the Drug Combination

General Information of Drug Combination (ID: DC6B6SG)

Drug Combination Name
Metoclopramide Propofol
Indication
Disease Entry Status REF
PREGNANCY Phase 1 [1]
Component Drugs Metoclopramide   DMFA5MY 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 Metoclopramide
Disease Entry ICD 11 Status REF
Nausea MD90 Approved [2]
Metoclopramide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Antagonist [6]
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Metoclopramide Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [7]
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Metoclopramide Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [8]
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Metoclopramide Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [9]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Decreases Expression [10]
Lutropin subunit beta (LHB) OT5GBOVJ LSHB_HUMAN Increases Expression [11]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [12]
Pro-glucagon (GCG) OTXU08VF GLUC_HUMAN Increases Secretion [13]
Insulin (INS) OTZ85PDU INS_HUMAN Increases Expression [14]
Gastric inhibitory polypeptide (GIP) OTUFSTG9 GIP_HUMAN Increases Secretion [13]
5-hydroxytryptamine receptor 3A (HTR3A) OTAIV1AK 5HT3A_HUMAN Decreases Activity [15]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Response [17]
Alpha-1D adrenergic receptor (ADRA1D) OTW2CD1O ADA1D_HUMAN Increases Response [18]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Propofol
Disease Entry ICD 11 Status REF
Anaesthesia 9A78.6 Approved [3]
Leukemia N.A. Approved [4]
Traumatic brain injury NA07.Z Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [5]
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 [21]
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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 [22]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [23]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [24]
Cytochrome P450 2A6 (CYP2A6) DEJVYAZ CP2A6_HUMAN Metabolism [25]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [26]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [23]
Cytochrome P450 2C18 (CYP2C18) DEZMWRE CP2CI_HUMAN Metabolism [25]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [25]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [22]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [27]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [25]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [28]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DESD26P UD16_HUMAN Metabolism [29]
Oleamide hydrolase 1 (FAAH) DEUM1EX FAAH1_HUMAN Metabolism [30]
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⏷ Show the Full List of 14 DME(s)
Propofol Interacts with 58 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Carbonic anhydrase 1 (CA1) OTNFBVVQ CAH1_HUMAN Decreases Activity [31]
Carbonic anhydrase 2 (CA2) OTJRMUAG CAH2_HUMAN Decreases Activity [31]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Activity [32]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [32]
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Expression [32]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [32]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [32]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Expression [32]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [32]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [32]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [32]
Leucine-rich colipase-like protein 1 (LRCOL1) OTDXBZF8 LRCL1_HUMAN Decreases Expression [20]
Glutamate dehydrogenase 1, mitochondrial (GLUD1) OTXKOCUH DHE3_HUMAN Decreases Expression [33]
Progonadoliberin-1 (GNRH1) OTH8A44K GON1_HUMAN Increases Expression [34]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Secretion [35]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [34]
Interleukin-2 receptor subunit alpha (IL2RA) OT0MWCHG IL2RA_HUMAN Decreases Secretion [36]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Increases Expression [34]
Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) OTTLGRGH GNAI2_HUMAN Decreases Expression [20]
Insulin-like growth factor I (IGF1) OTIIZR61 IGF1_HUMAN Increases Expression [34]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [37]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [34]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [34]
Small ribosomal subunit protein uS2 (RPSA) OTJZHEGT RSSA_HUMAN Increases Expression [34]
Matrilysin (MMP7) OTVT3SEJ MMP7_HUMAN Increases Expression [34]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) OTA675TJ GTR1_HUMAN Decreases Expression [33]
Proliferating cell nuclear antigen (PCNA) OTHZ1RIA PCNA_HUMAN Decreases Expression [20]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Increases Expression [34]
Metalloproteinase inhibitor 2 (TIMP2) OT8S1RRP TIMP2_HUMAN Increases Expression [34]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Increases Expression [37]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [33]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [33]
Ephrin type-B receptor 2 (EPHB2) OT8VZ6C5 EPHB2_HUMAN Increases Expression [34]
3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2) OTTG0NFD S5A2_HUMAN Decreases Expression [20]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [20]
Macrosialin (CD68) OTOYEY3J CD68_HUMAN Increases Expression [34]
Carbonic anhydrase 5A, mitochondrial (CA5A) OTP9M7VW CAH5A_HUMAN Decreases Expression [20]
Pigment epithelium-derived factor (SERPINF1) OTWZH98J PEDF_HUMAN Increases Expression [33]
Serine/threonine-protein kinase mTOR (MTOR) OTHH8KU7 MTOR_HUMAN Decreases Phosphorylation [20]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [33]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [33]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [20]
C-X-C chemokine receptor type 4 (CXCR4) OTUFSBX2 CXCR4_HUMAN Decreases Expression [33]
Protein SET (SET) OTGYYQJO SET_HUMAN Decreases Expression [34]
RNA-binding protein EWS (EWSR1) OT7SRHV3 EWS_HUMAN Increases Expression [34]
Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5) OTU4DD4G MGT5A_HUMAN Increases Expression [34]
Interleukin-18 (IL18) OTBB2A8O IL18_HUMAN Increases Expression [34]
Mothers against decapentaplegic homolog 2 (SMAD2) OTC6VB4K SMAD2_HUMAN Decreases Expression [34]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Expression [33]
Transmembrane channel-like protein 6 (TMC6) OTKH50J4 TMC6_HUMAN Increases Expression [20]
Polycystin-1-like protein 3 (PKD1L3) OTQMYNOW PK1L3_HUMAN Decreases Expression [20]
Uncharacterized protein C10orf67, mitochondrial (C10ORF67) OTX24W0H CJ067_HUMAN Increases Expression [20]
Sodium-coupled neutral amino acid transporter 3 (SLC38A3) OTCHH25G S38A3_HUMAN Decreases Expression [20]
Oxidoreductase HTATIP2 (HTATIP2) OT9MZ4QO HTAI2_HUMAN Increases Expression [34]
Pinin (PNN) OT0HXICH PININ_HUMAN Decreases Expression [34]
Protein turtle homolog B (IGSF9B) OTNOMYYQ TUTLB_HUMAN Decreases Expression [20]
Heparanase (HPSE) OTPTK5VS HPSE_HUMAN Increases Expression [34]
Mitochondrial pyruvate carrier 1 (MPC1) OT6DYFUO MPC1_HUMAN Decreases Expression [33]
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⏷ Show the Full List of 58 DOT(s)

References

1 ClinicalTrials.gov (NCT01781377) Prophylactic Subhypnotic Propofol for Nausea and Vomiting During for Cesarean Section Under Subarachnoid Anesthesia.
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: 241).
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: 5464).
4 Propofol FDA Label
5 Propofol and sedation in patients with coronavirus disease. Am J Emerg Med. 2020 Jun 18;S0735-6757(20)30512-X.
6 Mechanisms for metoclopramide-mediated sensitization and haloperidol-induced catalepsy in rats. Eur J Pharmacol. 2008 Jun 10;587(1-3):181-6.
7 Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
8 Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica. 2014 Apr;44(4):309-319.
9 Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
10 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
11 Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
12 Growth hormone and prolactin secretion after metoclopramide administration (DA2 receptor blockade) in fertile women. Horm Metab Res. 2001 Sep;33(9):536-9. doi: 10.1055/s-2001-17214.
13 Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion. Am J Physiol Gastrointest Liver Physiol. 2010 Dec;299(6):G1326-33. doi: 10.1152/ajpgi.00476.2009. Epub 2010 Sep 9.
14 Effect of drugs interacting with the dopaminergic receptors on glucose levels and insulin release in healthy and type 2 diabetic subjects. Am J Ther. 2008 Jul-Aug;15(4):397-402. doi: 10.1097/MJT.0b013e318160c353.
15 Interactions of metoclopramide and ergotamine with human 5-HT(3A) receptors and human 5-HT reuptake carriers. Br J Pharmacol. 2005 Oct;146(4):543-52. doi: 10.1038/sj.bjp.0706351.
16 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.
17 Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Jpn J Clin Oncol. 2011 Oct;41(10):1168-76. doi: 10.1093/jjco/hyr117. Epub 2011 Aug 11.
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19 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.
20 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.
21 Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
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27 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
28 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.
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31 Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols bioorg. Med Chem. 2009 Apr 15;17(8):3207-11.
32 Evaluation of cytotoxicity of propofol and its related mechanism in glioblastoma cells and astrocytes. Environ Toxicol. 2017 Dec;32(12):2440-2454.
33 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.
34 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.
35 Propofol withdrawal seizures (or not). Seizure. 2008 Oct;17(7):665-7. doi: 10.1016/j.seizure.2008.03.004. Epub 2008 May 14.
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 The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function. Br J Anaesth. 2006 Dec;97(6):825-31. doi: 10.1093/bja/ael270. Epub 2006 Oct 9.