General Information of Drug Combination (ID: DC13ILI)

Drug Combination Name
Maprotiline Atenolol
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Maprotiline   DMPWB7T Atenolol   DMNKG1Z
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 19
Bliss Independence Score: 19
Loewe Additivity Score: 25.8
LHighest Single Agent (HSA) Score: 25.85

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Maprotiline
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [2]
Major depressive disorder 6A70.3 Approved [3]
Mixed anxiety and depressive disorder N.A. Investigative [2]
Maprotiline Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [6]
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Maprotiline Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
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Maprotiline Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [8]
Beclin-1 (BECN1) OT4X293M BECN1_HUMAN Increases Expression [9]
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Indication(s) of Atenolol
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [4]
Hypertension BA00-BA04 Approved [5]
Malignant essential hypertension BA00 Approved [4]
Myocardial infarction BA41-BA43 Approved [4]
Atenolol 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 [11]
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Atenolol Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [13]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [14]
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Atenolol Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [15]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [16]
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Atenolol Interacts with 27 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases ADR [8]
Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) OT8SPJNX KCNQ1_HUMAN Affects Response To Substance [17]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [18]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [19]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [20]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [21]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Decreases Expression [22]
Apolipoprotein A-II (APOA2) OTQ3HGTC APOA2_HUMAN Decreases Expression [22]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Expression [22]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Increases Expression [23]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Increases Expression [24]
Reduced folate transporter (SLC19A1) OTWB0BTO S19A1_HUMAN Decreases Expression [25]
Sodium- and chloride-dependent creatine transporter 1 (SLC6A8) OT88C8JA SC6A8_HUMAN Decreases Expression [10]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Decreases Expression [26]
Small nuclear ribonucleoprotein-associated protein N (SNRPN) OTQB1ID1 RSMN_HUMAN Increases Expression [10]
Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5) OT404F9K FKBP5_HUMAN Decreases Expression [10]
Solute carrier organic anion transporter family member 4C1 (SLCO4C1) OTVILUUN SO4C1_HUMAN Increases Expression [10]
C-type lectin domain family 2 member B (CLEC2B) OT0W0M0L CLC2B_HUMAN Increases Expression [10]
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases Activity [27]
Inward rectifier potassium channel 2 (KCNJ2) OT2OQEZS KCNJ2_HUMAN Affects Response To Substance [17]
Voltage-dependent L-type calcium channel subunit alpha-1C (CACNA1C) OT6KFNMS CAC1C_HUMAN Increases Response To Substance [28]
Sodium channel protein type 5 subunit alpha (SCN5A) OTGYZWR6 SCN5A_HUMAN Increases ADR [8]
B2 bradykinin receptor (BDKRB2) OTOA9D3W BKRB2_HUMAN Affects Response To Substance [29]
Endothelin-1 (EDN1) OTZCACEG EDN1_HUMAN Affects Response To Substance [30]
Alpha-2A adrenergic receptor (ADRA2A) OTZFGOTP ADA2A_HUMAN Affects Response To Substance [31]
Potassium voltage-gated channel subfamily E member 1 (KCNE1) OTZNQUW9 KCNE1_HUMAN Increases ADR [8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Increases ADR [8]
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⏷ Show the Full List of 27 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Maprotiline FDA Label
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Atenolol FDA Label
5 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: 548).
6 Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
7 Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
8 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.
9 The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.
10 Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response. Arch Drug Inf. 2009 Sep;2(3):41-50. doi: 10.1111/j.1753-5174.2009.00020.x.
11 Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6.
12 Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500.
13 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.
14 Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol. 2010 Nov;70(5):645-55.
15 Metabolism of atenolol in man. Xenobiotica. 1978 May;8(5):313-20.
16 Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432.
17 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.
18 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
19 Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension. J Renin Angiotensin Aldosterone Syst. 2008 Sep;9(3):163-75. doi: 10.1177/1470320308096411.
20 Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Cardiovasc Pharmacol. 2003 Dec;42(6):719-26. doi: 10.1097/00005344-200312000-00005.
21 Atenolol improves ventricular function without changing plasma noradrenaline but decreasing plasma atrial natriuretic factor in chronic heart failure. Auton Autacoid Pharmacol. 2002 Oct-Dec;22(5-6):261-8. doi: 10.1046/j.1474-8673.2002.00266.x.
22 The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. Am Heart J. 1990 Jul;120(1):172-9. doi: 10.1016/0002-8703(90)90175-w.
23 Atenolol-induced regulation of leukocyte beta 2-adrenoceptors in hypertension. Pharmacology. 1984;29(4):210-4. doi: 10.1159/000138015.
24 A comparison of atenolol and nebivolol in isolated systolic hypertension. J Hypertens. 2008 Feb;26(2):351-6. doi: 10.1097/HJH.0b013e3282f283c9.
25 Folic acid uptake by the human syncytiotrophoblast: interference by pharmacotherapy, drugs of abuse and pathological conditions. Reprod Toxicol. 2009 Dec;28(4):511-20. doi: 10.1016/j.reprotox.2009.07.001. Epub 2009 Jul 16.
26 A 1-year follow-up study on the effect of atenolol on serum beta 2-microglobulin level in hypertensive diabetic patients. J Int Med Res. 1989 Mar-Apr;17(2):162-7. doi: 10.1177/030006058901700208.
27 Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation. 2003 May 20;107(19):2459-66. doi: 10.1161/01.CIR.0000068316.53218.49. Epub 2003 May 12.
28 CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response. Circ Cardiovasc Genet. 2009 Aug;2(4):362-70. doi: 10.1161/CIRCGENETICS.109.857839. Epub 2009 Jun 3.
29 B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens. 2003 Mar;21(3):621-4. doi: 10.1097/00004872-200303000-00029.
30 Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Clin Cardiol. 2004 May;27(5):287-90. doi: 10.1002/clc.4960270510.
31 Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment. J Hypertens. 2004 Dec;22(12):2321-8. doi: 10.1097/00004872-200412000-00014.