Effects of Repeated Administration of KW-3902, a Novel Adenosine A₁-Receptor Antagonist, on Its Pharmacological Actions

Abstract

Effects of repeated administration of KW-3902, a novel adenosine A₁-receptor antagonist, on its pharmacological actions were studied with regards to: 1) in vivo adenosine A₁-antagonism, 2) diuretic effects and 3) renal protective effects against glycerol-induced acute renal failure (ARF). After repeated oral administration of KW-3902 (0.1 mg/kg/day) for 24 days, neither enhancement of the sensitivity to 5''-N-ethylcarboxamidoadenosine (NECA) nor reduction of the inhibitory effect of KW-3902 on the NECA-induced bradycardic response were observed. After repeated oral administration of KW-3902 (0.01 and 0.1 mg/kg/day) for 20 days, the diuretic effects of KW-3902 did not change. Renal protective effects against glycerol-induced ARF were not reduced by repeated oral administration of KW-3902 (0.01 and 0.1 mg/kg/day) for 23 days. These results suggest that repeated oral administration of KW-3902 has no effect on its pharmacological actions. Additionally, changes in serum parameters, which occurred after repeated administration of furosemide or trichlormethiazide, were minimal after repeated oral administration of KW-3902 (0.001-1 mg/kg/day) for 27 days. From these results, KW-3902 proved to be a diuretic which has renal protective effects with less side effects.