PSC 833 is a non-immunosuppressant derivative of cyclosporine and potent multidrug-resistance (MDR) modulator. It restores sensitivity of MDR-P388 murine leukemia cells to cytostatic agents when used at concentrations of 70, 33, 45, 34, and 26 nM in combination with colchicine, vincristine , daunorubicin , doxorubicin , and etoposide , respectively. PSC 833 inhibits basal-to-apical transport and increases apical-to-basal transport of [14C]docetaxel in LLC-GA5-COLO150 cells that overexpress human P-glycoprotein (P-gp). In vivo, PSC 833 increases survival time in MDR-P388 tumor-bearing mice and in an MDR-L1210 leukemia mouse xenograft model when administered in combination with doxorubicin. PSC 833 also prolongs the anti-hyperalgesic effects of intraperitoneally administered pregabalin in a mouse model of cold stress-induced central pain.
