PT  - JOURNAL ARTICLE
AU  - David P. Brooks
AU  - Maurizio Valente
AU  - Giuseppe Petrone
AU  - P. Dennis Depalma
AU  - Massimo Sbacchi
AU  - Geoffrey D. Clarke
TI  - Comparison of the Water Diuretic Activity of <em>Kappa</em>Receptor Agonists and a Vasopressin Receptor Antagonist in Dogs
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1176--1183
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1176.short
4100  - http://jpet.aspetjournals.org/content/280/3/1176.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
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