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Protective effects of FK453, a potent nonxanthine adenosine A 1 receptor antagonist, on glycerol‐induced acute renal failure in rats
Author(s) -
Terai Takao,
Kusunoki Takahiro,
Kita Yasuhiro,
Nakano Keiko,
Nishioriko,
Kohno Yutaka,
Horiai Haruo,
Yoshida Keizo,
Mine Yasuhiro
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(19960901)39:1<47::aid-ddr6>3.0.co;2-k
Subject(s) - chemistry , furosemide , endocrinology , creatinine , medicine , antagonist , theophylline , hydrochlorothiazide , blood urea nitrogen , adenosine receptor , pharmacology , receptor , agonist , blood pressure
The purpose of the present study was to examine the protective effect of FK453, (+)‐(R)‐1‐[(E)‐3‐(2‐phenylpyrazolo [1,5‐a] pyridin‐3‐yl) acryloyl]‐2‐piperidine ethanol, a potent non‐xanthine (adenosine A 1 receptor antagonist, on glycerol‐induced acute renal failure (ARF) in rat in comparison with the effects of FR113452 (S‐(‐) enantiomer of FK453), 1,3‐dipropyl‐8‐cyclopentyl‐xanthine (adenosine A 1 receptor antagonist), theophylline (nonselective adenosine receptor antagonist), CGS15943 [1,2,4] triazolo [1,5‐C] quinazolone, adenosine A 2A receptor antagonist), and typical diuretics (hydrochlorothiazide and furosemide). FK453 (1 and 10 mg/kg orally) significantly reduced serum creatinine and urea concentrations in 25% glycerol (10 ml/kg intramuscularly)‐induced ARF by protective treatment. The effect was similar to that of 1,3‐dipropyl‐8‐cyclopentyl‐xanthine and theophylline. FR113452 and CGS15943 had little effect on serum creatinine and urea concentrations. In contrast, hydrochlorothiazide and furosemide increased serum creatinine and urea concentrations. FK453, hydrochlorothiazide, and furosemide did not have any effect on either serum creatinine or urea concentration in 25% glycerol‐induced ARF by therapeutic treatment. In 50% glycerol (10 ml/kg im)‐induced ARF, FK453 reduced serum creatinine and urea concentrations, and increased urine volume and creatinine clearance. The results of the present study showed that FK453, a potent nonxanthine adenosine A 1 receptor antagonist, ameliorated glycerol‐induced ARF in the rat. The findings support the idea that adenosine is an important factor in the development of glycerol‐induced ARF in the rat and that the protective effect of adenosine receptor antagonist is mediated via the adenosine A 1 receptor. Drug Dev. Res. 39:47–53 © 1997 Wiley‐Liss, Inc.