Diuretic Effects of KW-3902 (8-(Noradamantan-3-yl)-1,3-dipropylxanthine), a Novel Adenosine A_1 Receptor Antagonist, in Conscious Dogs

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The diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A_1 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 A_1 receptor blockade by KW-3902 causes consistent diuresis and natriuresis in dogs and suggest that adenosine A_1 receptor blockade is a promising approach to diuretic therapy.
社団法人日本薬学会の論文
1993-12-15