scholarly journals Evaluation of the Pharmacokinetics of Trazpiroben (TAK-906), a Peripherally Selective D2/D3 Dopamine Receptor Antagonist, in the Presence and Absence of Itraconazole, a Potent CYP 3A4 Inhibitor

2021 ◽  
Vol Volume 13 ◽  
pp. 145-155
Author(s):  
Chunlin Chen ◽  
Wenwen Zhang ◽  
Muhammad Bari ◽  
Cristina Almansa ◽  
Mike Baratta ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Dopamine Receptor Antagonist ◽  
Presence And Absence

Spectrofluorimetric determination of dopamine receptor antagonist LE 300 in mice plasma

Luminescence ◽  
2015 ◽  
Vol 31 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Mohamed Hefnawy ◽  
Mostafa Mohamed ◽  
Mohamed Abunassif ◽  
Amer Alanazi ◽  
Abdulrahman Al-Majed ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Dopamine Receptor Antagonist ◽  
Spectrofluorimetric Determination

scholarly journals The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

2020 ◽  
Vol 117 (20) ◽  
pp. 11085-11096 ◽  
Author(s):  
Kruttika Bhat ◽  
Mohammad Saki ◽  
Erina Vlashi ◽  
Fei Cheng ◽  
Sara Duhachek-Muggy ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Mouse Models ◽  
Radiation Sensitivity ◽  
Adult Brain ◽  
Continuous Treatment ◽  
Cell Phenotype ◽  
Dopamine Receptor Antagonist ◽  
Radiation Induced

Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

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