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Effect of fenoldopam prodrug, SK&F R‐105058, on renal function in rats
Author(s) -
Sakamoto Takashi,
Lokhandwala Mustafa F.
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430260107
Subject(s) - fenoldopam , prodrug , chemistry , natriuresis , endocrinology , pharmacology , diuresis , medicine , renal physiology , kidney , renal function , agonist , receptor , biochemistry
Recent development of and studies on fenoldopam prodrugs have shown their prolonged hemodynamic effects. This study was carried out in order to examine the effect of a fenoldopam prodrug on renal function in rats. In the present study we administered SK&F R‐105058, the 4′,7,8‐tris‐N‐ethyl carbamate ester of R‐fenoldopam, at a dose of 30 μg/kg/min intravenously to the anesthetized rats. This prodrug produced long‐lasting increases in water and sodium excretion after termination of the 30‐min drug infusion with minimum changes in hemodynamic parameters. The diuresis and natriuresis were attenuated in the presence of a selective DA 1 receptor antagonist SCH 23390. Therefore, it is suggested that production of fenoldopam from its precursor drug SK&F R‐105058 caused these prolonged renal effects, which were mediated via the activation of DA 1 receptors located on renal tubules. © 1992 Wiley‐Liss, Inc.