Details of the Drug Combination

General Information of Drug Combination (ID: DCXKHL5)

• Drug Combination Name: Ergonovine + Oxytocin
• Indication: Postpartum Hemorrhage; Status: Phase 1 [1]
• Component Drugs:
  Ergonovine (DM0VEC1): Small molecular drug
  Oxytocin (DMDL27I): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ergonovine

Disease Entry	ICD 11	Status	REF
Postpartum haemorrhage	JA43	Approved	[2]

Ergonovine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[7]

Ergonovine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Ergonovine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases ADR	[9]

Indication(s) of Oxytocin

Disease Entry	ICD 11	Status	REF
Autism spectrum disorder	6A02	Approved	[3]
Ductal breast carcinoma in situ	N.A.	Approved	[4]
Postpartum haemorrhage	JA43	Approved	[4]
Lactation failure	JB46.3	Phase 3	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[6]

Oxytocin Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vasopressin V1b receptor (V1BR)	TTL9MHW	V1BR_HUMAN	Agonist	[10]
Vasopressin V2 receptor (V2R)	TTK8R02	V2R_HUMAN	Agonist	[11]
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Agonist	[12]
Oxytocin receptor (OTR)	TTSCIUP	OXYR_HUMAN	Modulator	[13]

Oxytocin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Krueppel-like factor 4 (KLF4)	OT4O9RQW	KLF4_HUMAN	Increases Expression	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Cesarean Section Complications	DC8MZXF	N. A.	Phase 1	[15]

References

• [1] ClinicalTrials.gov (NCT06285409) Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium
• [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: 148).
• [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: 2174).
• [4] Oxytocin FDA Label
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039450)
• [6] Phase II RCT to Assess Efficacy of Intravenous Administration of Oxytocin in Patients Affected by COVID-19 (OsCOVID19)
• [7] Agonist profile of ergometrine (ergonovine) on a population of postsynaptic alpha-adrenoceptors. J Pharm Pharmacol. 1988 Feb;40(2):137-9.
• [8] Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions. World J Gastroenterol. 2007 Nov 14;13(42):5618-28.
• [9] 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.
• [10] The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinology. 1997 Oct;138(10):4109-22.
• [11] 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. (Target id: 368).
• [12] Mapping peptide-binding domains of the human V1a vasopressin receptor with a photoactivatable linear peptide antagonist. J Biol Chem. 1997 Oct 17;272(42):26536-44.
• [13] 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. (Target id: 369).
• [14] Oxytocin inhibits ox-LDL-induced adhesion of monocytic THP-1 cells to human brain microvascular endothelial cells. Toxicol Appl Pharmacol. 2017 Dec 15;337:104-110. doi: 10.1016/j.taap.2017.10.022. Epub 2017 Nov 2.
• [15] ClinicalTrials.gov (NCT03578263) Carbetocin Versus Oxytocin and Ergometrine for the Prevention of Postpartum Hemorrhage