RT Journal Article SR Electronic T1 Comparison of the Water Diuretic Activity of KappaReceptor Agonists and a Vasopressin Receptor Antagonist in Dogs JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1176 OP 1183 VO 280 IS 3 A1 David P. Brooks A1 Maurizio Valente A1 Giuseppe Petrone A1 P. Dennis Depalma A1 Massimo Sbacchi A1 Geoffrey D. Clarke YR 1997 UL http://jpet.aspetjournals.org/content/280/3/1176.abstract AB Strategies for developing selective water diuretic agents have involved development of kappa opioid receptor agonists and vasopressin V2 receptor antagonists; however, these two classes of compounds have not been compared directly. We have investigated the activity of three kappa receptor agonists and one nonpeptide vasopressin receptor antagonist in conscious dogs. SB 215520, SB 215519 and niravoline are selective kappaagonists with variable abilities to cause a water diuresis and ataxia in rats. When administered to conscious hydropenic dogs, thekappa agonists resulted in an increase in free water clearance; however, these effects were associated with an antinatriuresis, an increase in heart rate and, at the higher doses, central nervous system side effects. Conversely, the vasopressin receptor antagonist, OPC 31260, resulted in a significant water diuresis without any accompanying changes in sodium excretion and heart rate, and with no apparent central nervous system effects. These studies suggest that, at least in dogs, a vasopressin receptor antagonist is a more selective water diuretic than akappa receptor agonist. The American Society for Pharmacology and Experimental Therapeutics