Details of the Drug Combination

General Information of Drug Combination (ID: DC1PHPP)

• Drug Combination Name: Diazepam + Ondansetron
• Indication: Cataract; Status: Phase 1 [1]
• Component Drugs:
  Diazepam (DM08E9O): Small molecular drug
  Ondansetron (DMOTQ1I): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Diazepam

Disease Entry	ICD 11	Status	REF
Alcohol withdrawal	N.A.	Approved	[2]
Alcohol withdrawal delirium	N.A.	Approved	[2]
Anxiety	N.A.	Approved	[2]
Epilepsy	8A60-8A68	Approved	[3]
Tetanus	1C13	Investigative	[2]

Diazepam Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Agonist	[7]

Diazepam Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

Diazepam Interacts with 10 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[12]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Metabolism	[13]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[14]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[15]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[16]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[17]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[18]

Diazepam Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aldo-keto reductase family 1 member C4 (AKR1C4)	OTW2MMOF	AK1C4_HUMAN	Decreases Activity	[19]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[19]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[19]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[19]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[6]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[20]
Transforming growth factor beta-3 proprotein (TGFB3)	OT2LOUQ1	TGFB3_HUMAN	Decreases Expression	[6]
Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1)	OTC2W96H	GBRA1_HUMAN	Affects Activity	[21]
Biglycan (BGN)	OT3AV6IF	PGS1_HUMAN	Increases Expression	[6]
Collagen alpha-1(VII) chain (COL7A1)	OT3MIRZJ	CO7A1_HUMAN	Decreases Expression	[6]
Transforming growth factor beta receptor type 3 (TGFBR3)	OTQOOUC4	TGBR3_HUMAN	Decreases Expression	[6]
Fibromodulin (FMOD)	OT9EJ5H8	FMOD_HUMAN	Decreases Expression	[6]
Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2)	OTGNDWUO	GBRG2_HUMAN	Affects Response To Substance	[22]

Indication(s) of Ondansetron

Disease Entry	ICD 11	Status	REF
Chemotherapy-induced nausea	MD90	Approved	[4]
Malignant glioma	2A00.0	Approved	[5]
Nausea	MD90	Approved	[5]
Vomiting	MD90	Approved	[5]
Alcohol dependence	6C40.2	Phase 2	[4]
Gastroenteritis	N.A.	Investigative	[5]

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	[23]

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	[24]

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	[25]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[26]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[27]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[28]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[29]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[28]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[17]

References

• [1] ClinicalTrials.gov (NCT03653520) Conscious Sedation Efficacy of the MKO Melt (Midazolam, Ketamine, Ondansetron)
• [2] Diazepam FDA Label
• [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: 3364).
• [4] 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).
• [5] Ondansetron FDA Label
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• [12] Drug Interactions Flockhart Table
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• [20] The three recombinant domains of human serum albumin. Structural characterization and ligand binding properties. J Biol Chem. 1999 Oct 8;274(41):29303-10. doi: 10.1074/jbc.274.41.29303.
• [21] GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. Psychopharmacology (Berl). 2005 Jul;180(2):191-205. doi: 10.1007/s00213-005-2212-8. Epub 2005 Apr 28.
• [22] Heterogeneity of GABA(A) receptor-mediated responses in the human IMR-32 neuroblastoma cell line. J Neurosci Res. 2000 May 15;60(4):504-10. doi: 10.1002/(SICI)1097-4547(20000515)60:4<504::AID-JNR9>3.0.CO;2-Y.
• [23] 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.
• [24] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [25] The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999 Apr;65(4):377-81.
• [26] Effects of serotonin-3 receptor antagonists on cytochrome P450 activities in human liver microsomes. Biol Pharm Bull. 2006 Sep;29(9):1931-5.
• [27] 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.
• [28] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos. 1995 Nov;23(11):1225-30.
• [29] 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.