A prevalent form of multidrug resistance (MDR) in cancer cells is caused by an ATP-dependent drug efflux pump; this pump catalyzes the rapid exit of cytotoxic chemotherapy drugs from the cells. The Michaelis equation can be used to describe drug efflux through the MDR pump at a low drug substrate concentration [S]. The inhibition mechanism of an MDR reversal agent can be characterized when two different values of [S] are used to determine two values for the half-inhibition of efflux through the pump (I50). The reaction is noncompetitive when the two values of I50 are identical; the reaction is competitive when an increase in [S] produces a significant increase in the value of I50. The I50 has been determined for several different reversal agents with the substrate rhodamine 123. The inhibition potency observed is: cyclosporin A > DMDP > amiodarone > verapamil > quinidine > quinine > propranolol. Chemotherapy drugs that are potent inhibitors of the MDR pump could be used for the treatment of MDR neoplasia.

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