Flurazeparn inhibits the P-glycoprotein transport function: An insight to revert multidrug-resistance phenotype

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Sofia A C Lima (Author) Other; Joana Tavares (Author) FFUP; Paula Gameiro (Author) FCUP; Baltazar de Castro (Author) FCUP; Anabela Cordeiro da Silva (Author) FFUP

Journal

Title: European Journal of Pharmacology

Vol. 581 No. 1

Pages: 30-36

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 9 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-1F5

DOI: 10.1016/j.ejphar.2007.11.045

Abstract (EN): P-glycoprotein mediated drug transport may lead to a multidrug resistance phenotype often associated with a poor response to the successful treatment of a variety of human disorders. Several agents have been found to modulate P-glycoprotein drug resistance, most probably by blocking its transport function. The aim of this study was to examine the effects of some benzodiazepines (bromazepam, chlordiazepoxide, diazepam and flurazepam) able to bind to P-glycoprotein in proteoliposomes on its transport function and ATPase activity in the human cancer cell line, KB-V1. The toxicity of the benzodiazepines drugs towards KB-V1 cells was first evaluated and the non toxic drugs concentrations were used to assess the drug efflux and the ATPase activity. Using the flow cytometry approach, the accumulation and efflux of daunorubicin were followed by measuring the daunorubicin associated geometric mean fluorescence intensity. Vanadate was employed as a comparative inhibitory compound. Flurazepam was able to inhibit the daunorubicin efflux in 80%. ATPase activity determined by a colorimetric assay revealed that flurazepam inhibits the P-glycoprotein enzymatic activity, indicating coupling between drug transport and ATP hydrolysis. Bromazepam, chlordiazepoxide and diazepam behaved as activators of the P-glycoprotein ATPase activity, suggesting a role as transported substrates and did not interfere in the daunorubicin transport.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7