LACIDIPINE AND JOSAMYCIN - 2 NEW MULTIDRUG-RESISTANCE MODULATORS

In this paper we report the results obtained treating a multidrug resi stant (MDR) murine erythroleukemia cell line with daunomycin (DNM) in association with two new modulators characterized by a favourable ther apeutic index, lacidipine (LCD), a dihydropyridine calcium antagonist, and josamycin (JSM), a macrolide antibiotic. LCD and JSM exhibited a greater MDR reversal activity than verapamil (VRP) and erythromycin (E RY) respectively. The accumulation of DNM in the DRTL cells exposed to modulators was similar to that of the parental cell line FLC. In the case of LCD, it was possible to ascertain that at a very low concentra tion this molecule can circumvent MDR without modifying DNM accumulati on, suggesting that multiple different determinants may responsible fo r MDR other than P-170 in this cell line.