General Information of Drug Combination (ID: DCFLM1J)

Drug Combination Name
Ziprasidone Olanzapine
Indication
Disease Entry Status REF
Schizophrenia Phase 1 [1]
Component Drugs Ziprasidone   DMM58JY Olanzapine   DMPFN6Y
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 Ziprasidone
Disease Entry ICD 11 Status REF
Bipolar disorder 6A60 Approved [2]
Schizoaffective disorder 6A21 Approved [2]
Schizophrenia 6A20 Approved [3]
Ziprasidone Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Neuronal acetylcholine receptor alpha-7 (CHRNA7) TTLA931 ACHA7_HUMAN Binder [3]
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Agonist [6]
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Ziprasidone Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
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Ziprasidone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [8]
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Ziprasidone Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [9]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [9]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [9]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [11]
Transcription factor SOX-17 (SOX17) OT9H4WWE SOX17_HUMAN Decreases Localization [12]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Olanzapine
Disease Entry ICD 11 Status REF
Bipolar depression N.A. Approved [4]
Major depressive disorder 6A70.3 Approved [4]
Schizoaffective disorder 6A21 Approved [4]
Schizophrenia 6A20 Approved [5]
Olanzapine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Agonist [14]
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Olanzapine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [15]
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Olanzapine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [16]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [17]
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Olanzapine Interacts with 63 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Decreases Activity [18]
D(2) dopamine receptor (DRD2) OTBLXKEG DRD2_HUMAN Increases Response To Substance [19]
Lathosterol oxidase (SC5D) OT41KMW4 SC5D_HUMAN Increases Expression [9]
Low-density lipoprotein receptor (LDLR) OTH559LU LDLR_HUMAN Increases Expression [9]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases Expression [9]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) OTCO26FV HMCS1_HUMAN Increases Expression [9]
Long-chain fatty acid transport protein 2 (SLC27A2) OT7JEG5F S27A2_HUMAN Increases Expression [20]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [21]
Ceruloplasmin (CP) OTM8JE4Y CERU_HUMAN Affects Phosphorylation [22]
Prothrombin (F2) OTNFSM49 THRB_HUMAN Affects Phosphorylation [22]
Complement factor B (CFB) OTZITNEJ CFAB_HUMAN Affects Phosphorylation [22]
Alpha-1-antichymotrypsin (SERPINA3) OT9BP2S0 AACT_HUMAN Increases Phosphorylation [22]
Alpha-2-macroglobulin (A2M) OTFTX90K A2MG_HUMAN Affects Phosphorylation [22]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Affects Phosphorylation [22]
Complement C5 (C5) OTSL3OIC CO5_HUMAN Affects Phosphorylation [22]
Kininogen-1 (KNG1) OT4X9LDE KNG1_HUMAN Affects Phosphorylation [22]
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Increases Expression [23]
Insulin (INS) OTZ85PDU INS_HUMAN Increases Expression [24]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Phosphorylation [22]
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Phosphorylation [22]
Complement component C9 (C9) OT7I5FDX CO9_HUMAN Affects Phosphorylation [22]
Beta-2-glycoprotein 1 (APOH) OTFMUX6O APOH_HUMAN Affects Phosphorylation [22]
Fibronectin (FN1) OTB5ZN4Q FINC_HUMAN Affects Phosphorylation [22]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Phosphorylation [22]
Vitamin D-binding protein (GC) OTWS63BY VTDB_HUMAN Affects Phosphorylation [22]
Hemopexin (HPX) OT14T7Q1 HEMO_HUMAN Affects Phosphorylation [22]
Apolipoprotein B-100 (APOB) OTH0UOCZ APOB_HUMAN Increases Phosphorylation [22]
Histidine-rich glycoprotein (HRG) OTPLUFOG HRG_HUMAN Affects Phosphorylation [22]
Alpha-1B-glycoprotein (A1BG) OTFVUGNQ A1BG_HUMAN Affects Phosphorylation [22]
Sex hormone-binding globulin (SHBG) OTPWU5IW SHBG_HUMAN Decreases Expression [25]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Expression [26]
Plasma protease C1 inhibitor (SERPING1) OT6CVN45 IC1_HUMAN Affects Phosphorylation [22]
Apolipoprotein A-IV (APOA4) OT466POQ APOA4_HUMAN Affects Phosphorylation [22]
Fatty acid-binding protein, liver (FABP1) OTR34ETM FABPL_HUMAN Increases Expression [20]
Complement factor H (CFH) OTAGKQTJ CFAH_HUMAN Decreases Phosphorylation [22]
Complement C4-A (C4A) OTXMOYXU CO4A_HUMAN Decreases Phosphorylation [22]
Clusterin (CLU) OTQGG0JM CLUS_HUMAN Affects Phosphorylation [22]
Muscarinic acetylcholine receptor M1 (CHRM1) OTKW3E6B ACM1_HUMAN Affects Binding [27]
Complement component C6 (C6) OTCKR304 CO6_HUMAN Affects Phosphorylation [22]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4) OTJZG0LD GLUT4_HUMAN Increases Expression [28]
Inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2) OTG3WBBE ITIH2_HUMAN Affects Phosphorylation [22]
Brain-derived neurotrophic factor (BDNF) OTLGH7EW BDNF_HUMAN Increases Expression [29]
5-hydroxytryptamine receptor 2A (HTR2A) OTWXJX0M 5HT2A_HUMAN Affects Binding [27]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Increases Expression [30]
Histamine H1 receptor (HRH1) OT8F9FV6 HRH1_HUMAN Affects Binding [27]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Increases Expression [24]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1) OTNBHULA PACR_HUMAN Affects Expression [13]
Afamin (AFM) OTPOR8IO AFAM_HUMAN Affects Phosphorylation [22]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Decreases Expression [30]
5-hydroxytryptamine receptor 6 (HTR6) OT8GTDDY 5HT6R_HUMAN Affects Binding [27]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [31]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Expression [26]
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) OT460OO1 ITIH4_HUMAN Affects Phosphorylation [22]
Long-chain fatty acid transport protein 5 (SLC27A5) OT4OK511 S27A5_HUMAN Increases Expression [20]
D(3) dopamine receptor (DRD3) OT0OFFKB DRD3_HUMAN Increases ADR [32]
5-hydroxytryptamine receptor 1A (HTR1A) OT38K9MK 5HT1A_HUMAN Increases Response [33]
5-hydroxytryptamine receptor 2C (HTR2C) OT6H8DE0 5HT2C_HUMAN Increases Response To Substance [34]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Response To Substance [35]
Aquaporin-4 (AQP4) OTA9MYD5 AQP4_HUMAN Increases Response To Substance [36]
D(4) dopamine receptor (DRD4) OTAJTO7N DRD4_HUMAN Increases ADR [32]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases ADR [32]
Methylenetetrahydrofolate reductase (MTHFR) OTUBJSR7 MTHR_HUMAN Affects Response To Substance [37]
Synaptosomal-associated protein 25 (SNAP25) OTUIQ81Q SNP25_HUMAN Affects Response To Substance [38]
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⏷ Show the Full List of 63 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hyperglycemia DCW7IXX N. A. Phase 1 [39]
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References

1 ClinicalTrials.gov (NCT01185743) Antipsychotics and Gene Expression in Soft Tissues
2 Ziprasidone FDA Label
3 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
4 Olanzapine 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: 47).
6 Striatal and extrastriatal D2/D3-receptor-binding properties of ziprasidone: a positron emission tomography study with [18F]Fallypride and [11C]raclopride (D2/D3-receptor occupancy of ziprasidone). JClin Psychopharmacol. 2008 Dec;28(6):608-17.
7 Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
8 Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8.
9 Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs. BMC Neurosci. 2006 Oct 20;7:69.
10 Opposite clozapine and ziprasidone effects on the reactivity of plasma albumin SH-group are the consequence of their different binding properties dependent on protein fatty acids content. Chem Biol Interact. 2019 Sep 25;311:108787. doi: 10.1016/j.cbi.2019.108787. Epub 2019 Aug 7.
11 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
12 A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
13 Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors. Neurochem Res. 2017 Apr;42(4):943-952. doi: 10.1007/s11064-016-2127-2. Epub 2016 Nov 30.
14 Olanzapine: an updated review of its use in the management of schizophrenia. Drugs. 2001;61(1):111-61.
15 Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
16 Interactions between the cytochrome P450 system and the second-generation antipsychotics. J Psychiatry Neurosci. 2003 Mar;28(2):99-112.
17 [Olanzapine: pharmacology, pharmacokinetics and therapeutic drug monitoring]. Fortschr Neurol Psychiatr. 2001 Nov;69(11):510-7.
18 Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
19 Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment. Pharmacogenet Genomics. 2010 Jun;20(6):359-66. doi: 10.1097/FPC.0b013e3283397d06.
20 Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019 Nov;316:183-193. doi: 10.1016/j.toxlet.2019.08.013. Epub 2019 Aug 19.
21 In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs. Chem Res Toxicol. 2012 Aug 20;25(8):1616-32. doi: 10.1021/tx300091x. Epub 2012 May 31.
22 Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. Proteomics Clin Appl. 2015 Oct;9(9-10):907-16. doi: 10.1002/prca.201400148. Epub 2015 May 15.
23 The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. Clin Ther. 2000 Sep;22(9):1085-96. doi: 10.1016/S0149-2918(00)80086-7.
24 Recovery from new-onset diabetes in a schizophrenic man after withdrawal of olanzapine. Psychosomatics. 2002 Jan-Feb;43(1):67-70. doi: 10.1176/appi.psy.43.1.67.
25 Hormonal markers of metabolic dysregulation in patients with severe mental disorders after olanzapine treatment under real-life conditions. J Clin Psychopharmacol. 2009 Apr;29(2):109-16. doi: 10.1097/JCP.0b013e31819b95fc.
26 Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients. J Clin Psychopharmacol. 2005 Oct;25(5):419-26. doi: 10.1097/01.jcp.0000177668.42640.fe.
27 No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. doi: 10.1038/sj.tpj.6500418. Epub 2006 Sep 19.
28 Effects of different antipsychotics and the antidepressant mirtazapine on glucose transporter mRNA levels in human blood cells. J Psychiatr Res. 2006 Jun;40(4):374-9. doi: 10.1016/j.jpsychires.2005.04.016. Epub 2005 Jul 5.
29 The differential effects of neuroleptic drugs and PACAP on the expression of BDNF mRNA and protein in a human glioblastoma cell line. Acta Neurobiol Exp (Wars). 2017;77(3):205-213.
30 Famotidine has a neuroprotective effect on MK-801 induced toxicity via the Akt/GSK-3/-catenin signaling pathway in the SH-SY5Y cell line. Chem Biol Interact. 2019 Dec 1;314:108823. doi: 10.1016/j.cbi.2019.108823. Epub 2019 Sep 26.
31 Effects of cyamemazine on hERG, INa, ICa, Ito, Isus and IK1 channel currents, and on the QTc interval in guinea pigs. Eur J Pharmacol. 2006 Feb 27;532(3):270-8. doi: 10.1016/j.ejphar.2005.12.079. Epub 2006 Feb 21.
32 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.
33 Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia. Adv Ther. 2010 May;27(5):307-13. doi: 10.1007/s12325-010-0035-4. Epub 2010 Jun 8.
34 Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene. Pharmacogenomics J. 2009 Aug;9(4):234-41. doi: 10.1038/tpj.2009.18. Epub 2009 May 12.
35 DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia. Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1158-63. doi: 10.1073/pnas.1013535108. Epub 2010 Dec 27.
36 Different impacts of aquaporin 4 and MAOA allele variation among olanzapine, risperidone, and paliperidone in schizophrenia. J Clin Psychopharmacol. 2012 Jun;32(3):394-7. doi: 10.1097/JCP.0b013e31825370f4.
37 MTHFR and risk of metabolic syndrome in patients with schizophrenia. Schizophr Res. 2010 Aug;121(1-3):193-8. doi: 10.1016/j.schres.2010.05.030. Epub 2010 Jun 12.
38 The SNAP-25 gene may be associated with clinical response and weight gain in antipsychotic treatment of schizophrenia. Neurosci Lett. 2005 May 6;379(2):81-9. doi: 10.1016/j.neulet.2004.12.037. Epub 2005 Jan 26.
39 ClinicalTrials.gov (NCT00910988) Healthy Volunteers Study of the Effects of Olanzapine and Ziprasidone