Inhibitory effect of 1,4-dimorpholino-7-phenylpyrido[3,4-d]-pyridazine (DS-511) and its 4'-hydroxy derivative on antidiuretic action of vasopressin in rats.
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.
D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D004232:Diuretics; D009025:Morpholines; D011724:Pyridazines; D006852:Hydrochlorothiazide; D014667:Vasopressins; D005665:Furosemide