R-dl-verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin

AIM: To study the attenuation of multidrug resistance (MDR) by R-dl-verapam il (R-Ver) and the acute animal toxicity of R-Ver, and to compare these res ults of R-Ver with the results of dl-verapamil (Ver). METHODS: Cytotoxicity was determined by tetrazolium (MIT) assay. Cellular accumulation of doxoru bicin (Dox) was measured by fluorescence spectrophotometry. Acute animal to xicity was tested by ip drug administration in BALB/c mice. RESULTS: R-Ver attenuated MDR of KBv200 cells to vincristine (VCR) and Dox. This attenuati on ability was dose-related, and was also dependent on drug exposure time. R-Ver 1.25 mu mol . L-1 increased the sensitivity of KBv200 cells to VCR (P < 0.01) with a 24-h period of drug exposure. R-Ver downmodulated MDR and i ncreased cellular Dox accumulation of KBv200 cells as effectively as Ver, b ut possessed lower acute toxicity in BALB/c mice. While LD50 Of Ver was 60 (49 - 73) mg . kg(-1), LD50 of R-Ver was 166 (137 - 202) mg . kg(-1). CONCL USION: R-Ver downmodulated the MDR to VCR and Dox at 1.25 mu mol . L-1, and this effect on VCR can be realized with drug exposure duration of 24 h.