COMPARISON OF THE WATER DIURETIC ACTIVITY OF KAPPA-RECEPTOR AGONISTS AND A VASOPRESSIN RECEPTOR ANTAGONIST IN DOGS

Strategies for developing selective water diuretic agents have involve d development of kappa opioid receptor agonists and vasopressin V2 rec eptor antagonists; however, these two classes of compounds have not be en compared directly. We have investigated the activity of three kappa receptor agonists and one nonpeptide vasopressin receptor antagonist in conscious dogs. SE 215520, SE 215519 and niravoline are selective k appa agonists with variable abilities to cause a water diuresis and at axia in rats. When administered to conscious hydropenic dogs, the kapp a agonists resulted in an increase in free water clearance; however, t hese effects were associated with an antinatriuresis, an increase in h eart rate and, at the higher doses, central nervous system side effect s, Conversely, the vasopressin receptor antagonist, OPC 31260, resulte d 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 vasopr essin receptor antagonist is a more selective water diuretic than a ka ppa receptor agonist.