YM 872

Zonampanel inhibits the human MRP4-mediated transport of [ ³ H]oestradiol 17-D-glucuronide in a concentration-dependent manner. In contrast, Zonampanel (up to 1000 mM) does not inhibit the human MRP2- or BCRP-mediated transport of [ ³ H]oestradiol 17-D-glucuronide or [ ³ H]methotrexate. Zonampanel inhibits the uptake of typical substrates by Oat1, Oat2, and Oat3 with inhibition constant (K _i ) values of 7.02 to 10.4 μM. A time- and saturable concentration-dependent increase in [ ¹⁴ C]Zonampanel uptake is observed in these cells [K _m values: 13.4 to 53.6 μM].

In in vivo experiments, probenecid and cimetidine decrease intrinsic clearance for both the renal secretion and biliary excretion of Zonampanel.