Details of the Drug Combination

General Information of Drug Combination (ID: DC448PB)

Drug Combination Name
Propranolol Salbutamol
Indication
Disease Entry Status REF
Pulmonary Disease, Chronic Obstructive Phase 1 [1]
Component Drugs Propranolol   DM79NTF Salbutamol   DMN9CWF
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Propranolol
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [2]
Atrial fibrillation BC81.3 Approved [2]
Cocaine addiction 6C45.2 Approved [2]
Hemangioma 2E81-2F2Y Approved [2]
Migraine 8A80 Approved [3]
Respiratory papillomatosis 2F00.1 Investigative [2]
Propranolol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-1 (ADRB1) TTR6W5O ADRB1_HUMAN Antagonist [8]
------------------------------------------------------------------------------------
Propranolol Interacts with 4 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [10]
Organic cation transporter 3 (SLC22A3) DT6201N S22A3_HUMAN Substrate [10]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [10]
------------------------------------------------------------------------------------
Propranolol Interacts with 8 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [14]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [14]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [15]
Dimethylaniline oxidase 2 (FMO2) DEIASEZ FMO2_HUMAN Metabolism [16]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 DME(s)
Propranolol Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Oxidation [18]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Oxidation [18]
Flavin-containing monooxygenase 2 (FMO2) OTUJUL9S FMO2_HUMAN Increases Oxidation [16]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [19]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [20]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Affects Response To Substance [21]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [7]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [7]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [7]
Angiopoietin-2 (ANGPT2) OTEQK65P ANGP2_HUMAN Decreases Expression [22]
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [23]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [24]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [25]
Insulin (INS) OTZ85PDU INS_HUMAN Decreases Expression [26]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Expression [27]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [22]
Ornithine decarboxylase (ODC1) OTNDAGRR DCOR_HUMAN Increases Activity [28]
Beta-adrenergic receptor kinase 1 (GRK2) OT34KKWK ARBK1_HUMAN Decreases Expression [29]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [30]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [31]
Proliferation marker protein Ki-67 (MKI67) OTA8N1QI KI67_HUMAN Decreases Expression [22]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Decreases Expression [30]
G protein-activated inward rectifier potassium channel 1 (KCNJ3) OTHQG16J KCNJ3_HUMAN Increases Expression [27]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [31]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [32]
ADP-ribosylation factor 6 (ARF6) OTVV7KJO ARF6_HUMAN Affects Localization [33]
Angiopoietin-1 receptor (TEK) OT78YN57 TIE2_HUMAN Decreases Expression [22]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [22]
Delta-like protein 4 (DLL4) OTRA4K2V DLL4_HUMAN Decreases Expression [30]
Inward rectifier potassium channel 2 (KCNJ2) OT2OQEZS KCNJ2_HUMAN Affects Response To Substance [21]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases ADR [34]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Oxidation [18]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Increases ADR [34]
Potassium voltage-gated channel subfamily E member 1 (KCNE1) OTZNQUW9 KCNE1_HUMAN Increases ADR [34]
------------------------------------------------------------------------------------
⏷ Show the Full List of 34 DOT(s)
Indication(s) of Salbutamol
Disease Entry ICD 11 Status REF
Acute asthma CA23 Approved [4]
Adult respiratory distress syndrome CB00 Approved [5]
Severe asthma CA23 Approved [6]
Salbutamol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor beta-2 (ADRB2) TT2CJVK ADRB2_HUMAN Agonist [35]
------------------------------------------------------------------------------------
Salbutamol 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 [36]
------------------------------------------------------------------------------------
Salbutamol Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [37]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Metabolism [38]
Sulfotransferase 1A3 (SULT1A3) DEP7E8X ST1A3_HUMAN Metabolism [39]
------------------------------------------------------------------------------------
Salbutamol Interacts with 24 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Response To Substance [40]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Increases Expression [41]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Increases Expression [42]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Expression [43]
Insulin (INS) OTZ85PDU INS_HUMAN Increases Expression [44]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [45]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [45]
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Decreases Expression [45]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [46]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Expression [47]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Expression [48]
Creatine kinase M-type (CKM) OTME0KO7 KCRM_HUMAN Increases Secretion [49]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [46]
Cyclin-dependent kinase 4 (CDK4) OT7EP05T CDK4_HUMAN Increases Expression [47]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Increases Expression [47]
Platelet-activating factor receptor (PTAFR) OT2133DF PTAFR_HUMAN Increases Expression [47]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Expression [47]
Serum paraoxonase/arylesterase 1 (PON1) OTD0Z2XO PON1_HUMAN Decreases Activity [50]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [45]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [46]
Interleukin-24 (IL24) OT4VUWH1 IL24_HUMAN Increases Expression [45]
Hepatic sodium/bile acid cotransporter (SLC10A1) OTUJVMCL NTCP_HUMAN Increases Expression [42]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [45]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Affects Response To Substance [51]
------------------------------------------------------------------------------------
⏷ Show the Full List of 24 DOT(s)

References

1 ClinicalTrials.gov (NCT00549120) Optimising the Propranolol Block Model
2 Propranolol 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: 7596).
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: 558).
5 Effects of nebulized salbutamol on respiratory mechanics in adult respiratory distress syndrome. Intensive Care Med. 1997 Jan;23(1):58-64.
6 Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial. Pediatr Pulmonol. 2019 Apr;54(4):372-377.
7 beta2-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NFB and AP-1. Cancer Biol Ther. 2010 Jul 1;10(1):19-29.
8 Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
9 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
10 Influx Transport of Cationic Drug at the Blood-Retinal Barrier: Impact on the Retinal Delivery of Neuroprotectants. Biol Pharm Bull. 2017;40(8):1139-1145.
11 Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos. 1994 Nov-Dec;22(6):909-15.
12 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
13 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
14 The influence of diltiazem versus cimetidine on propranolol metabolism. J Clin Pharmacol. 1992 Dec;32(12):1099-104.
15 Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol. 2001 Oct;52(4):349-55.
16 Human FMO2-based microbial whole-cell catalysts for drug metabolite synthesis. Microb Cell Fact. 2015 Jun 12;14:82.
17 acillus megaterium SF185 spores exert protective effects against oxidative stress in vivo and in vitro. Sci Rep. 2019 Aug 19;9(1):12082.
18 Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys. Chem Biol Interact. 2010 Jan 5;183(1):67-78. doi: 10.1016/j.cbi.2009.10.007.
19 Rapid induction of P-glycoprotein expression by high permeability compounds in colonic cells in vitro: a possible source of transporter mediated drug interactions?. Biochem Pharmacol. 2004 Aug 15;68(4):783-90. doi: 10.1016/j.bcp.2004.05.006.
20 Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
21 Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome. J Cardiovasc Electrophysiol. 2004 Feb;15(2):190-9. doi: 10.1046/j.1540-8167.2004.03212.x.
22 Propranolol inhibits proliferation and induces apoptosis of hemangioma-derived endothelial cells via Akt pathway by down-regulating Ang-2 expression. Chem Biol Interact. 2020 Jan 25;316:108925. doi: 10.1016/j.cbi.2019.108925. Epub 2019 Dec 12.
23 Development of a common carp (Cyprinus carpio) pregnane X receptor (cPXR) transactivation reporter assay and its activation by azole fungicides and pharmaceutical chemicals. Toxicol In Vitro. 2017 Jun;41:114-122. doi: 10.1016/j.tiv.2017.02.023. Epub 2017 Mar 1.
24 Intrapatient comparison of treatment with chlorthalidone, spironolactone and propranolol in normoreninemic essential hypertension. Am J Cardiol. 1975 Oct 31;36(5):716-21. doi: 10.1016/0002-9149(75)90174-5.
25 Labetalol (AH5158), a competitive alpha- and beta-receptor blocking drug, in the management of hypertension. Aust N Z J Med. 1976 Aug;6(3 Suppl):83-8. doi: 10.1111/j.1445-5994.1976.tb03341.x.
26 Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia. Am J Physiol. 1986 Sep;251(3 Pt 1):E322-7. doi: 10.1152/ajpendo.1986.251.3.E322.
27 Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines. BMC Cancer. 2004 Dec 16;4:93. doi: 10.1186/1471-2407-4-93.
28 Adrenergic modulation of cardiac development in the rat: effects of prenatal exposure to propranolol via continuous maternal infusion. J Dev Physiol. 1990 May;13(5):243-9.
29 Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation. 1998 Oct 27;98(17):1783-9. doi: 10.1161/01.cir.98.17.1783.
30 Propranolol inhibits proliferation and invasion of hemangioma-derived endothelial cells by suppressing the DLL4/Notch1/Akt pathway. Chem Biol Interact. 2018 Oct 1;294:28-33. doi: 10.1016/j.cbi.2018.08.018. Epub 2018 Aug 18.
31 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
32 Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: the study of beta-adrenoceptor antagonist's anticancer effect in pancreatic cancer cell. Pancreas. 2009 Jan;38(1):94-100. doi: 10.1097/MPA.0b013e318184f50c.
33 An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling. Mol Biol Cell. 2006 Jan;17(1):327-35. doi: 10.1091/mbc.e05-06-0523. Epub 2005 Nov 9.
34 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.
35 Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). CNS Drugs. 2002;16(1):1-8.
36 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.
37 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
38 Effect of carboxylesterase 1 c.428G>A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8.
39 SULT 1A3 single-nucleotide polymorphism and the single dose pharmacokinetics of inhaled salbutamol enantiomers: are some athletes at risk of higher urine levels? Drug Test Anal. 2015 Feb;7(2):109-13.
40 beta2-adrenergic receptor polymorphisms and salbutamol-stimulated energy expenditure. J Clin Endocrinol Metab. 2005 Apr;90(4):2301-7. doi: 10.1210/jc.2004-1356. Epub 2005 Feb 1.
41 Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds. Toxicol Appl Pharmacol. 2007 Dec 1;225(2):142-53.
42 Carvedilol impairs bile acid homeostasis in mice: implication for nonalcoholic steatohepatitis. Toxicol Sci. 2023 Nov 28;196(2):200-217. doi: 10.1093/toxsci/kfad088.
43 Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers. Br J Clin Pharmacol. 1987 Nov;24(5):645-53. doi: 10.1111/j.1365-2125.1987.tb03224.x.
44 A prospective study of the effects of prolonged timolol therapy on alpha- and beta-adrenoceptor and angiotensin II receptor mediated responses in normal subjects. Br J Clin Pharmacol. 1997 Mar;43(3):301-8. doi: 10.1111/j.1365-2125.1997.00559.x.
45 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
46 [Role of salbutamol in inducing apoptosis of cultured human airway smooth muscle cells]. Zhonghua Jie He He Hu Xi Za Zhi. 2001 Apr;24(4):219-24.
47 Mechanisms by which S-albuterol induces human bronchial smooth muscle cell proliferation. Int Arch Allergy Immunol. 2008;146(4):321-33. doi: 10.1159/000121466. Epub 2008 Mar 21.
48 Levalbuterol inhibits human airway smooth muscle cell proliferation: therapeutic implications in the management of asthma. Int Arch Allergy Immunol. 2006;139(3):225-36. doi: 10.1159/000091168. Epub 2006 Jan 27.
49 Elevation of creatine kinase from skeletal muscle associated with inhaled albuterol. Ann Allergy Asthma Immunol. 1996 Dec;77(6):488-90. doi: 10.1016/S1081-1206(10)63356-X.
50 Association of human serum paraoxonase-1 with some respiratory drugs. J Biochem Mol Toxicol. 2019 Dec;33(12):e22407. doi: 10.1002/jbt.22407. Epub 2019 Oct 3.
51 Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment. BMC Cardiovasc Disord. 2004 Sep 28;4(1):16. doi: 10.1186/1471-2261-4-16.