Shibouta Y, Nishikawa K, Kikuchi S
Arzneimittelforschung. 1978;28(8):1398-403.
The water-diuretic features of 1,4-dimorpholino-7-phenylpyridol[3,4-d]-pyridazine (DS-511) and its water-soluble 4'-OH derivative [DS-511(4'-OH)] were investigated. In saline-infused rats the minimum i.v. diuretic dose of DS-511(4'-OH) was 1.0 micrograms/kg/min, while in water-diuretic rats the minimum dose was 50 micrograms/kg/min. Intravenous infusion of DS-511 or DS-511(4'-OH) at rates of 1 to 10 micrograms/kg/min caused a dose-dependent inhibition of the ADH-induced antidiuresis in water-diuretic rats, and a decrease in urinary osmolality. However, hydrochlorothiazide even at 500 micrograms/kg/min did not alter the antidiuresis, but increased the osmolality. Furosemide at a rate of 10 micrograms/kg/min increased urinary excretion of water and sodium in both saline-infused and water-diuretic rats, but the same dose did not inhibit the ADH-induced antidiuresis. These findings indicate that the specific anti-ADH action at relatively low doses of DS-511 and DS-511(4'-OH) is partly involved in the diuretic mechanism of these agents.
研究了1,4-二吗啉代-7-苯基吡啶并[3,4-d]哒嗪（DS-511）及其水溶性4'-羟基衍生物[DS-511(4'-OH)]的利水特性。在输注生理盐水的大鼠中，DS-511(4'-OH)的最小静脉注射利尿剂量为1.0微克/千克/分钟，而在水利尿大鼠中最小剂量为50微克/千克/分钟。以1至10微克/千克/分钟的速率静脉输注DS-511或DS-511(4'-OH)，会导致水利尿大鼠中抗利尿激素诱导的抗利尿作用出现剂量依赖性抑制，并使尿渗透压降低。然而，即使以500微克/千克/分钟的剂量使用氢氯噻嗪也不会改变抗利尿作用，但会增加渗透压。以10微克/千克/分钟的速率使用呋塞米会使输注生理盐水的大鼠和水利尿大鼠的水和钠的尿排泄量增加，但相同剂量不会抑制抗利尿激素诱导的抗利尿作用。这些发现表明，DS-511和DS-511(4'-OH)在相对低剂量下的特异性抗抗利尿激素作用部分参与了这些药物的利尿机制。
