title: 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.
authors.affiliation: Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kusaka
authors.forename: A
authors.initials: A
authors.lastname: Karasawa
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000284:Administration, Oral; D000818:Animals; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005665:Furosemide / Q000494:pharmacology; D005990:Glycerol / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014237:Trichlormethiazide / Q000494:pharmacology; D014554:Urination / Q000187:drug effects; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D004232:Diuretics; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); C073525:rolofylline; D005665:Furosemide; D000241:Adenosine; D005990:Glycerol; D014237:Trichlormethiazide