Yamagata T, Kobayashi T, Kusaka H, Karasawa A
Department of Pharmacology, Pharmaceutical Research Laboratories, Kogyo Co., Ltd., Shizuoka, Japan.
Biol Pharm Bull. 1994 Dec;17(12):1599-603. doi: 10.1248/bpb.17.1599.
The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume, urinary excretion of electrolytes and renal hemodynamics were examined in anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited the decline of renal blood flow induced by intrarenal arterial injection of adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant increases in urine volume and sodium excretion with little change in potassium excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min continued for longer than 1 h even after discontinuation of the KW-3902 infusion. KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought about significant increases in urine volume and excretion of sodium and potassium. The diuresis and saliuresis induced by furosemide continued for only 40 min after discontinuation of the drug infusion. Trichlormethiazide at 3 micrograms/kg/min for 20 min also provoked increases in urine volume and sodium excretion, but did not affect potassium excretion. The diuretic and natriuretic effect of trichlormethiazide gradually disappeared after discontinuation of the drug infusion. The present study in anesthetized dogs suggests that KW-3902, an adenosine A1-receptor antagonist, produces diuresis and natriuresis but not kaliuresis and that the diuresis and natriuresis are caused in large part by the inhibition of sodium reabsorption at tubular sites.
在麻醉犬中研究了新型腺苷A1受体拮抗剂KW-3902（8-（去甲金刚烷-3-基）-1,3-二丙基黄嘌呤）静脉输注对尿量、电解质尿排泄和肾血流动力学的影响。以10和30微克/千克/分钟的剂量静脉输注KW-3902 20分钟，可抑制肾内动脉注射腺苷（0.5-2.0微克）引起的肾血流量下降。这些剂量的KW-3902可显著增加尿量和钠排泄，而钾排泄变化不大。以30微克/千克/分钟的剂量静脉输注KW-3902 20分钟，即使在停止输注后，其利尿作用仍持续超过1小时。KW-3902不影响肌酐清除率、肾血流量、动脉血压或心率。以10微克/千克/分钟的剂量静脉输注速尿20分钟，可显著增加尿量以及钠和钾的排泄。停止药物输注后，速尿引起的利尿和利钠作用仅持续40分钟。以3微克/千克/分钟的剂量静脉输注三氯噻嗪20分钟，也可引起尿量和钠排泄增加，但不影响钾排泄。停止药物输注后，三氯噻嗪的利尿和利钠作用逐渐消失。在麻醉犬中进行的本研究表明，腺苷A1受体拮抗剂KW-3902可产生利尿和利钠作用，但不产生利钾作用，且利尿和利钠作用在很大程度上是由肾小管部位钠重吸收的抑制引起的。
