Potencies of mioflazine and its derivatives as inhibitors of adenosine transport in isolated erythrocytes from different species

Abstract

Abstract The potency of mioflazine and related drugs (Janssen Pharmaceutica, Belgium) as inhibitors of adenosine transport in isolated erythrocytes from several species were measured and compared with those of dilazep and 6-(4-nitrobenzylmercapto)purine ribonucleoside (NBMPR). [8−3H]Adenosine was used as the permeant at 1 μM and incubation times were 10 s, and assays were conducted in the presence and absence of varying doses of potential transport inhibitors. The species investigated included mouse, hamster, rabbit, baboon and man. Dilazep was the most potent compound throughout with an IC50 of about 2 nM. In the mouse and hamster mioflazine and its derivatives were considerably less potent (IC50 values > 200 nM) with the exception of R57974 with IC50 values of about 150 and 60 nM in mouse and hamster, respectively. In the man and baboon the derivatives had IC50 values in the same order of magnitude as NBMPR (< 100 nM), and in the rabbit they had potencies close to that of NBMPR, ranging between 10–60 nM. Nucleoside transport inhibitors are of potential importance as host protectors during treatment of parasitic infections with cytotoxic nucleosides. Present data indicate that mioflazine and its derivatives are not very potent in some of the preferred animal models for parasitic infections (mouse, hamster) but are more effective in primates such as man and baboon.