Details of the Drug Combination

General Information of Drug Combination (ID: DCB1LU4)

• Drug Combination Name: Oxytocin + Magnesium Sulfate
• Indication: Postpartum Hemorrhage; Status: Phase 1 [1]
• Component Drugs:
  Oxytocin (DMDL27I): Small molecular drug
  Magnesium Sulfate (DMVEK07): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Oxytocin

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

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	[8]
Vasopressin V2 receptor (V2R)	TTK8R02	V2R_HUMAN	Agonist	[9]
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Agonist	[10]
Oxytocin receptor (OTR)	TTSCIUP	OXYR_HUMAN	Modulator	[11]

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	[12]

Indication(s) of Magnesium Sulfate

Disease Entry	ICD 11	Status	REF
Acute pain	MG31	Approved	[6]
Familial primary hypomagnesemia	N.A.	Approved	[7]
Hypertension, pregnancy-induced	N.A.	Approved	[7]
Mild pre-eclampsia	N.A.	Approved	[7]
Non-arteritic anterior ischemic optic neuropathy	9C40.40	Approved	[7]
Pain	MG30-MG3Z	Approved	[7]
Severe pre-eclampsia	N.A.	Approved	[7]
Traumatic brain injury	NA07.Z	Approved	[7]

Magnesium Sulfate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Antagonist	[13]

Magnesium Sulfate Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Kallikrein-8 (KLK8)	OTGVGHXY	KLK8_HUMAN	Increases Activity	[14]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[15]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[16]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[16]

References

• [1] ClinicalTrials.gov (NCT02647268) Effect of Magnesium Sulphate Pre-exposure on Oxytocin-induced Contractility in Desensitized Human Myometrium - an in Vitro Study
• [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: 2174).
• [3] Oxytocin FDA Label
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800039450)
• [5] Phase II RCT to Assess Efficacy of Intravenous Administration of Oxytocin in Patients Affected by COVID-19 (OsCOVID19)
• [6] Emerging drugs for acute ischemic stroke. Expert Opin Emerg Drugs. 2009 Mar;14(1):33-42.
• [7] Magnesium Sulfate FDA Label
• [8] The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinology. 1997 Oct;138(10):4109-22.
• [9] 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).
• [10] 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.
• [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: 369).
• [12] 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.
• [13] Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block. Reg Anesth Pain Med. 2007 Jul-Aug;32(4):288-95.
• [14] Activation and enzymatic characterization of recombinant human kallikrein 8. Biol Chem. 2006 Jun;387(6):723-31. doi: 10.1515/BC.2006.091.
• [15] Haemodynamic and endocrine effects of deliberate hypotension with magnesium sulphate for cerebral-aneurysm surgery. Eur J Anaesthesiol. 1991 Mar;8(2):115-21.
• [16] Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.