Details of the Drug Combination

General Information of Drug Combination (ID: DC2SEXK)

• Drug Combination Name: Norepinephrine + Phenylephrine
• Indication: Hypotension; Status: Phase 3 [1]
• Component Drugs:
  Norepinephrine (DMOUC09): Small molecular drug
  Phenylephrine (DMZHUO5): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Norepinephrine

Disease Entry	ICD 11	Status	REF
Alopecia	ED70	Approved	[2]
Bronchiectasis	CA24	Approved	[2]
Bronchitis	CA20	Approved	[2]
Chronic fatigue syndrome	8E49	Approved	[2]
Depression	6A70-6A7Z	Approved	[2]
Psychosexual disorder	N.A.	Approved	[2]
Pulmonary emphysema	CA21.Z	Approved	[2]
Pure autonomic failure	N.A.	Approved	[2]
Radiodermatitis	N.A.	Approved	[2]
Sepsis	1G40-1G41	Approved	[3]
Severe asthma	CA23	Approved	[2]
Asthma	CA23	Investigative	[2]

Norepinephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Stimulator	[8]

Norepinephrine Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[9]
Organic cation transporter 3 (SLC22A3)	DT6201N	S22A3_HUMAN	Substrate	[9]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]
Vesicular amine transporter 2 (SLC18A2)	DTT7VPB	VMAT2_HUMAN	Substrate	[11]
Vesicular amine transporter 1 (SLC18A1)	DTM953D	VMAT1_HUMAN	Substrate	[11]
Sodium-dependent noradrenaline transporter (SLC6A2)	DT9JBVI	SC6A2_HUMAN	Substrate	[12]
Sodium- and chloride-dependent glycine transporter 2 (SLC6A5)	DTE8R17	SC6A5_HUMAN	Substrate	[13]

Norepinephrine Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Decreases Activity	[14]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[15]
Sodium-dependent noradrenaline transporter (SLC6A2)	OTMHQJMP	SC6A2_HUMAN	Decreases Uptake	[16]
Protein phosphatase 1 regulatory subunit 12A (PPP1R12A)	OT4AVU95	MYPT1_HUMAN	Increases Phosphorylation	[17]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[18]
Protein S100-B (S100B)	OTHHDS33	S100B_HUMAN	Increases Expression	[19]
Protein S100-A8 (S100A8)	OTVMOB3F	S10A8_HUMAN	Increases Expression	[20]
Intercellular adhesion molecule 1 (ICAM1)	OTTOIX77	ICAM1_HUMAN	Increases Expression	[18]
Myosin light chain 1/3, skeletal muscle isoform (MYL1)	OTDUYR4U	MYL1_HUMAN	Increases Phosphorylation	[17]
Protein S100-A9 (S100A9)	OTOARHCS	S10A9_HUMAN	Increases Expression	[20]
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Affects Binding	[21]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Increases Expression	[21]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[21]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Increases Secretion	[22]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[18]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[21]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Affects Localization	[18]
Cannabinoid receptor 1 (CNR1)	OTEALO6G	CNR1_HUMAN	Affects Expression	[23]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Affects Binding	[24]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Affects Binding	[25]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Affects Localization	[18]
Proto-oncogene c-Rel (REL)	OTTCKMAC	REL_HUMAN	Affects Localization	[18]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Increases Uptake	[26]
Pro-neuropeptide Y (NPY)	OT4ICV3P	NPY_HUMAN	Affects Response To Substance	[27]
Amine oxidase A (MAOA)	OT8NIWMQ	AOFA_HUMAN	Increases Metabolism	[28]
Sulfotransferase 1A3 (SULT1A4)	OTHJ8WWV	ST1A3_HUMAN	Increases Sulfation	[29]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Increases Methylation	[30]
Neuron-specific vesicular protein calcyon (CALY)	OTQ7EMPU	CALY_HUMAN	Increases Secretion	[31]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Decreases Abundance	[32]
Equilibrative nucleoside transporter 4 (SLC29A4)	OTWTZXMX	S29A4_HUMAN	Increases Uptake	[15]

Indication(s) of Phenylephrine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[4]
Arrhythmia	BC9Z	Approved	[4]
Common cold	CA00	Approved	[4]
Cough	MD12	Approved	[4]
Fecal incontinence	ME07	Approved	[5]
Fever	MG26	Approved	[4]
Headache	8A80-8A84	Approved	[4]
Mydriasis	LA11.62	Approved	[4]
Ophthalmic graves disease	5A02.0	Approved	[6]
Proctitis	DB33.Z	Approved	[4]
Rhinitis	FA20	Approved	[4]
Seasonal allergic rhinitis	CA08.01	Approved	[4]
Vasomotor/allergic rhinitis	CA08	Approved	[4]

Phenylephrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[33]

Phenylephrine Interacts with 34 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Apoptosis-inducing factor 1, mitochondrial (AIFM1)	OTKPWB7Q	AIFM1_HUMAN	Increases Expression	[34]
Renin (REN)	OT52GZR2	RENI_HUMAN	Decreases Activity	[35]
Carbonic anhydrase 1 (CA1)	OTNFBVVQ	CAH1_HUMAN	Decreases Activity	[36]
Carbonic anhydrase 2 (CA2)	OTJRMUAG	CAH2_HUMAN	Decreases Activity	[36]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Expression	[37]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Secretion	[35]
Fibronectin (FN1)	OTB5ZN4Q	FINC_HUMAN	Increases Expression	[37]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[34]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[38]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Activity	[39]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases Activity	[39]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Activity	[39]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[40]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[34]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Affects Activity	[34]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[34]
Myosin regulatory light chain 2, atrial isoform (MYL7)	OT7ZNDP4	MLRA_HUMAN	Increases Phosphorylation	[41]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[34]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[34]
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1)	OTC41R1E	RIPK1_HUMAN	Increases Expression	[34]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Affects Activity	[34]
Nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4)	OTTDCUAO	NFAC4_HUMAN	Increases Localization	[42]
Mixed lineage kinase domain-like protein (MLKL)	OTDSLC81	MLKL_HUMAN	Increases Expression	[34]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Increases Expression	[34]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Affects Expression	[43]
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	OTL1D484	RIPK3_HUMAN	Increases Expression	[34]
Pro-adrenomedullin (ADM)	OT7T0TA4	ADML_HUMAN	Decreases Response To Substance	[44]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Response To Substance	[45]
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Affects Response To Substance	[46]
Plasma membrane calcium-transporting ATPase 4 (ATP2B4)	OTMWFDAC	AT2B4_HUMAN	Increases Response To Substance	[47]
Beta-3 adrenergic receptor (ADRB3)	OTPMG4V7	ADRB3_HUMAN	Increases Response To Substance	[48]
Lipoprotein lipase (LPL)	OTTW0267	LIPL_HUMAN	Affects Response To Substance	[49]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Response To Substance	[50]
Caveolin-3 (CAV3)	OTWSFDB4	CAV3_HUMAN	Decreases Response To Substance	[51]

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