Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1 receptor antagonist, in conscious dogs.
The diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1 receptor antagonist, were determined and compared with those of trichlormethiazide (TCM) and furosemide in saline-loaded conscious dogs. KW-3902, at doses higher than 0.1 mg/kg (p.o.), produced dose-dependent increases of urine volume and sodium excretion and these effects were statistically significant at doses of 1-100 mg/kg. The increase in potassium excretion was lower than that of sodium, and the ratio of sodium to potassium excretion (Na/K) tended to be elevated. TCM (0.3 mg/kg) and furosemide (3 mg/kg) also induced increases in urine volume and sodium excretion. The diuretic effects of KW-3902 lasted for 4 h after administration, whereas TCM and furosemide caused significant natriuresis for 2 h after administration. Thus, KW-3902 exhibited a longer lasting natriuresis than TCM and furosemide. These results indicate that adenosine A1 receptor blockade by KW-3902 causes consistent diuresis and natriuresis in dogs and suggest that adenosine A1 receptor blockade is a promising approach to diuretic therapy.
Kobayashi
T
T
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Mizumoto
H
H
Karasawa
A
A
D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D014237:Trichlormethiazide / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D004232:Diuretics; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D005665:Furosemide; D014237:Trichlormethiazide