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Naunyn Schmiedebergs Arch Pharmacol. 2009 Mar;379(3):263-70. doi: 10.1007/s00210-008-0358-8. Epub 2008 Oct 17.

Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A.

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  • 1Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA. sinan@temple.edu

Abstract

Kappa opioid receptor agonists induce water diuresis in animals and humans. We investigated the effects of s.c. nalfurafine, U50,488H, salvinorin A, and its longer-acting analog, 2-methoxymethyl-salvinorin B (MOM-sal B), on urinary output and sodium excretion over 5 h in euvolemic rats. Nalfurafine (0.005-0.02 mg/kg), U50,488H (0.1-10 mg/kg), and MOM-sal B (0.625-5 mg/kg) induced diuresis dose-dependently. Systemically (0.1-10 mg/kg) or centrally (50 microg, i.c.v.) administered salvinorin A was ineffective. 5'-Guanidinonaltrindole, a kappa receptor antagonist, inhibited nalfurafine- and MOM-sal B-induced diuresis. Nalfurafine and MOM-sal B had no effect on arginine vasopressin levels, measured at 2 h. Tolerance did not develop to the diuresis accompanying subchronic administration of nalfurafine (0.02 mg/kg). On the basis of our work, we (a) promote nalfurafine as a candidate diuretic to relieve water retention and (b) highlight salvinorin A as a kappa agonist that does not cause diuresis, probably because of its short duration of action.

PMID:
18925386
DOI:
10.1007/s00210-008-0358-8
[PubMed - indexed for MEDLINE]
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