General Information of Drug Combination (ID: DCCFI2K)

Drug Combination Name
Reboxetine Citalopram
Indication
Disease Entry Status REF
Schizophrenia Phase 1 [1]
Component Drugs Reboxetine   DM26PRD Citalopram   DM2G9AE
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 Reboxetine
Disease Entry ICD 11 Status REF
Depression 6A70-6A7Z Approved [2]
Major depressive disorder 6A70.3 Approved [3]
Pain MG30-MG3Z Approved [4]
Diabetic neuropathy 8C0Z Investigative [5]
Reboxetine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Norepinephrine transporter (NET) TTAWNKZ SC6A2_HUMAN Inhibitor [8]
------------------------------------------------------------------------------------
Reboxetine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
------------------------------------------------------------------------------------
Reboxetine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [10]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Decreases Expression [10]
------------------------------------------------------------------------------------
Indication(s) of Citalopram
Disease Entry ICD 11 Status REF
Acute coronary syndrome BA41 Approved [6]
Anxiety N.A. Approved [6]
Depression 6A70-6A7Z Approved [7]
Insomnia 7A00-7A0Z Approved [6]
Lung cancer 2C25.0 Approved [6]
Major depressive disorder 6A70.3 Approved [6]
Colon cancer 2B90.Z Investigative [6]
Gastric cancer 2B72 Investigative [6]
Citalopram Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serotonin transporter (SERT) TT3ROYC SC6A4_HUMAN Modulator [11]
------------------------------------------------------------------------------------
Citalopram Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [12]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [14]
------------------------------------------------------------------------------------
Citalopram Interacts with 4 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]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Metabolism [17]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [18]
------------------------------------------------------------------------------------
Citalopram Interacts with 29 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Methylation [19]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Methylation [19]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Methylation [20]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Response [21]
Glutamate receptor 3 (GRIA3) OT34CNBR GRIA3_HUMAN Affects Response To Substance [22]
Glutamate receptor ionotropic, kainate 2 (GRIK2) OTQ41U3D GRIK2_HUMAN Affects Response To Substance [22]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Expression [23]
Nuclear protein 1 (NUPR1) OT4FU8C0 NUPR1_HUMAN Increases Expression [24]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Expression [24]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [24]
Solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) OT2HZK5M GTR3_HUMAN Decreases Expression [24]
Inhibin beta E chain (INHBE) OTOI2NYG INHBE_HUMAN Increases Expression [24]
Transgelin (TAGLN) OTAEZ0KP TAGL_HUMAN Decreases Expression [24]
Lysophospholipase D GDPD3 (GDPD3) OTOHM9QM GDPD3_HUMAN Increases Expression [24]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Affects Binding [25]
Aromatase (CYP19A1) OTZ6XF74 CP19A_HUMAN Decreases Activity [26]
Stearoyl-CoA desaturase (SCD) OTB1073G SCD_HUMAN Increases Expression [27]
Pro-opiomelanocortin (POMC) OTV41F7T COLI_HUMAN Increases Expression [28]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [29]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [30]
Aryl hydrocarbon receptor (AHR) OTFE4EYE AHR_HUMAN Decreases Expression [31]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [27]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Expression [32]
Sodium-dependent dopamine transporter (SLC6A3) OT39XG28 SC6A3_HUMAN Affects Response To Substance [33]
Sodium-dependent serotonin transporter (SLC6A4) OT6FGDLW SC6A4_HUMAN Affects Response To Substance [34]
Glutamate receptor 1 (GRIA1) OT85LOCJ GRIA1_HUMAN Affects Response To Substance [22]
Glutamate receptor ionotropic, kainate 4 (GRIK4) OTL5EIPA GRIK4_HUMAN Increases Response [35]
Glutamate receptor ionotropic, NMDA 3A (GRIN3A) OTQS9GYY NMD3A_HUMAN Affects Response To Substance [22]
5-hydroxytryptamine receptor 2A (HTR2A) OTWXJX0M 5HT2A_HUMAN Increases Response [36]
------------------------------------------------------------------------------------
⏷ Show the Full List of 29 DOT(s)

References

1 ClinicalTrials.gov (NCT01300364) Reboxetine and Citalopram as an Adjunct Treatment to Second Generation Antipsychotics in the Treatment of Negative Symptoms of Schizophrenia
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: 4808).
3 Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366.
4 Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jul 13;109:110266.
5 Catecholaminergic and opioidergic system mediated effects of reboxetine on diabetic neuropathic pain. Psychopharmacology (Berl). 2020 Apr;237(4):1131-1145.
6 Citalopram FDA Label
7 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: 7547).
8 Reboxetine: the first selective noradrenaline re-uptake inhibitor. Expert Opin Pharmacother. 2000 May;1(4):771-82.
9 Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. Clin Pharmacokinet. 2000 Dec;39(6):413-27.
10 Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. Hypertension. 2006 Jul;48(1):120-6. doi: 10.1161/01.HYP.0000225424.13138.5d. Epub 2006 May 22.
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
12 MRP1 polymorphisms associated with citalopram response in patients with major depression. J Clin Psychopharmacol. 2010 Apr;30(2):116-25.
13 ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram. Int J Legal Med. 2013 May;127(3):579-86.
14 Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences. Drug Metab Pharmacokinet. 2008;23(4):243-53.
15 PharmGKB summary: citalopram pharmacokinetics pathway. Pharmacogenet Genomics. 2011 Nov;21(11):769-72.
16 Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69.
17 Antidepressant drugs in the elderly--role of the cytochrome P450 2D6. World J Biol Psychiatry. 2003 Apr;4(2):74-80.
18 Citalopram and desmethylcitalopram in vitro: human cytochromes mediating transformation, and cytochrome inhibitory effects. Biol Psychiatry. 1999 Sep 15;46(6):839-49.
19 Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics. 1997 Feb;7(1):1-10.
20 Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab Dispos. 2003 Oct;31(10):1255-9. doi: 10.1124/dmd.31.10.1255.
21 ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):398-404. doi: 10.1016/j.pnpbp.2007.09.003. Epub 2007 Sep 15.
22 Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology. 2009 Jun;34(7):1819-28. doi: 10.1038/npp.2009.4. Epub 2009 Mar 18.
23 Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment. Eur Arch Psychiatry Clin Neurosci. 2004 Aug;254(4):231-5.
24 In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies. Toxicol Sci. 2007 Sep;99(1):162-73.
25 Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
26 Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay. Toxicol In Vitro. 2015 Oct;29(7):1729-35.
27 Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006 Mar 13;395(3):185-90. doi: 10.1016/j.neulet.2005.10.096. Epub 2005 Dec 1.
28 Neuroendocrine effects of citalopram, a selective serotonin re-uptake inhibitor, during lifespan in humans. J Endocrinol Invest. 2010 Oct;33(9):657-62. doi: 10.1007/BF03346666. Epub 2010 Apr 22.
29 Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease. Brain. 2009 Feb;132(Pt 2):392-401. doi: 10.1093/brain/awn326. Epub 2009 Jan 19.
30 The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
31 Profiling of enantiopure drugs towards aryl hydrocarbon (AhR), glucocorticoid (GR) and pregnane X (PXR) receptors in human reporter cell lines. Chem Biol Interact. 2014 Feb 5;208:64-76. doi: 10.1016/j.cbi.2013.11.018. Epub 2013 Dec 6.
32 Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2). Gut. 2003 Feb;52(2):300-3. doi: 10.1136/gut.52.2.300.
33 Differential effects of psychoactive substances on human wildtype and polymorphic T356M dopamine transporters (DAT). Toxicology. 2019 Jun 15;422:69-75. doi: 10.1016/j.tox.2019.04.012. Epub 2019 Apr 19.
34 5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study. J Clin Psychopharmacol. 2003 Dec;23(6):563-7. doi: 10.1097/01.jcp.0000095350.32154.73.
35 Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry. 2007 Aug;164(8):1181-8. doi: 10.1176/appi.ajp.2007.06111790.
36 Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet. 2006 May;78(5):804-814. doi: 10.1086/503820. Epub 2006 Mar 20.