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Cardiovascular and Renal Hemodynamic Effects of A-68930 in the Conscious Dog: A Comparison With Fenoldopam

Cardiovascular and Renal Hemodynamic Effects of A-68930 in the Conscious Dog: A Comparison With Fenoldopam

M I Christie, G W Smith

J Pharmacol Exp Ther. 1994 Feb;268(2):565-70.

PMID: 7906731

Abstract:

The renal hemodynamic and cardiovascular effects of the novel dopamine (DA) D1 receptor agonist A-68930 (5-6-dihydroxy-3-phenyl-1-aminomethyl- isochroman hydrochloride) were studied in the chronically instrumented conscious dog. Intravenous infusion of A-68930, fenoldopam or DA produced a fall in renal vascular resistance and a rise in renal blood flow (RBF), with hypotension and tachycardia. Both compounds were more potent than DA at increasing RBF. By the i.v. route, A-68930 was calculated to be 12 times more potent than fenoldopam. At the end of a submaximal infusion, the effects of A-68930 on RBF declined with a half-time of 14.8 +/- 2.5 min, significantly longer than that of fenoldopam (2.9 +/- 0.5 min) or DA (1.4 +/- 0.4 min). After p.o. dosing, A-68930 was calculated to be 84 times more potent than fenoldopam at increasing RBF. Furthermore, the A-68930-induced increase in RBF took longer to return to base line (5-6 hr) than after an equieffective p.o. dose of fenoldopam (1-2 hr). The effects of p.o. A-68930 were blocked by the DA1 antagonist, SCH 23390 [7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-(1H)-3-benzazepine hydrochloride], consistent with an action at the DA1 receptor. These data indicate that A-68930 is a potent, p.o.-active DA1 agonist in the conscious dog with a longer duration of action than fenoldopam.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP130465393	A-68930 hydrochloride		130465-39-3	Price

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