Details of the Drug Combination

General Information of Drug Combination (ID: DC91J70)

• Drug Combination Name: Metoclopramide + Ondansetron
• Indication: Postoperative Pain; Status: Phase 4 [1]
• Component Drugs:
  Metoclopramide (DMFA5MY): Small molecular drug
  Ondansetron (DMOTQ1I): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

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	[5]

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	[6]

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	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Metoclopramide Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[8]
Pro-glucagon (GCG)	OTXU08VF	GLUC_HUMAN	Increases Secretion	[9]
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Decreases Activity	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response	[11]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Response	[12]

Indication(s) of Ondansetron

Disease Entry	ICD 11	Status	REF
Chemotherapy-induced nausea	MD90	Approved	[3]
Malignant glioma	2A00.0	Approved	[4]
Nausea	MD90	Approved	[4]
Vomiting	MD90	Approved	[4]
Alcohol dependence	6C40.2	Phase 2	[3]
Gastroenteritis	N.A.	Investigative	[4]

Ondansetron Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3 receptor (5HT3R)	TTNXLKE	NOUNIPROTAC	Agonist	[13]

Ondansetron Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]

Ondansetron Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[16]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[17]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[18]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[19]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[18]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[20]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Nausea	DC531GA	N. A.	Phase 4	[21]

References

• [1] ClinicalTrials.gov (NCT01837394) Ultrasound-guided Blocks for Ambulatory Knee Arthroscopy
• [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: 2290).
• [4] Ondansetron FDA Label
• [5] Mechanisms for metoclopramide-mediated sensitization and haloperidol-induced catalepsy in rats. Eur J Pharmacol. 2008 Jun 10;587(1-3):181-6.
• [6] 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.
• [7] Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6. Xenobiotica. 2014 Apr;44(4):309-319.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Clinical response and side effects of metoclopramide: associations with clinical, demographic, and pharmacogenetic parameters. J Clin Gastroenterol. 2012 Jul;46(6):494-503. doi: 10.1097/MCG.0b013e3182522624.
• [13] Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial. Eur J Gastroenterol Hepatol. 1998 Oct;10(10):865-70.
• [14] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [15] The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999 Apr;65(4):377-81.
• [16] Effects of serotonin-3 receptor antagonists on cytochrome P450 activities in human liver microsomes. Biol Pharm Bull. 2006 Sep;29(9):1931-5.
• [17] Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting. Med Sci Monit. 2005 Oct;11(10):RA322-8.
• [18] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos. 1995 Nov;23(11):1225-30.
• [19] Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos. 1996 May;24(5):602-9.
• [20] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [21] ClinicalTrials.gov (NCT02959840) Acupuncture Point P6 Stimulation for Reduction of Nausea and Vomiting During Cesarean