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Dopamine1 receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits

Dopamine1 receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits. Szabo, Bela; Hedler, Liselotte; Starke, Klaus (Pharmakol. Inst., Univ. Freiburg/Br., Freiburg/Br., Fed. Rep. Ger.). J. Pharmacol. Exp. Ther., 239(3), 881-6 (English) 1986. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Neurochem. and circulatory effects of fenoldopam [67227-56-9] were studied in pithed rabbits with elec. stimulated sympathetic outflow and in strips of the rabbit pulmonary artery. In pithed rabbits, fenoldopam (1-30 mg/kg/min) decreased the arterial blood pressure. Fenoldopam (3-30 mg/kg/min) also increased the norepinephrine spillover rate (the rate at which endogenous norepinephrine enters into the plasma after having been released from postganglionic sympathetic nerves) and decreased the [3H]norepinephrine plasma clearance. The selective dopamine (DA)1 antagonist SCH 23390 antagonized markedly and the DA2-selective antagonist domperidone antagonized slightly the hypotensive effect. The increase in the norepinephrine spillover rate was enhanced after treatment with desipramine. Clonidine reduced the spillover of norepinephrine, and this effect was abolished by fenoldopam. In pulmonary artery strips preincubated with [3H]norepinephrine, fenoldopam (10-7 and 10-6M) increased the elec. evoked overflow of tritium. The effct of fenoldopam (10-6M) was prevented in the presence of a supramaximal concn. of clonidine (10-5M). The results suggest that fenoldopam lowers blood pressure mainly by activation of vascular smooth muscle DA1 receptors. In addn., however, it blocks prejunctional alpha-2 autoreceptors at postganglionic sympathetic axons.

Evaluation of the effects of SKF 82526 and LY 171555 on presynaptic (DA2) and postsynaptic (DA1) dopamine receptors in rat kidney

Evaluation of the effects of SKF 82526 and LY 171555 on presynaptic (DA2) and postsynaptic (DA1) dopamine receptors in rat kidney. Lokhandwala, M. F.; Steenberg, M. L. (Coll. Pharm., Univ. Houston, Houston, TX 77004, USA). J. Auton. Pharmacol., 4(4), 273-7 (English) 1984. CODEN: JAPHDU. ISSN: 0144-1795. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 SKF 82526 [67227-56-9] failed to alter 3H-labeled noradrenaline [51-41-2] release elicited during periarterial nerve stimulation in isolated kidney, whereas LY 171555 (I) [88494-74-0] caused a concn.-dependent inhibition of the stimulus-induced release of [3H]noradrenaline. This inhibitory action of LY 171555 could be antagonized by sulpiride but not by SCH 23390. SKF 82526 caused concn.-dependent renal vasodilation which could be antagonized by SCH 23390. LY 171555 did not produce significant changes in renal perfusion pressure over a wide range of concns. Thus, SKF 82526 and LY 171555 are selective agonists at DA1 and DA2 receptors, resp. These agents represent an important class of compds. that would be useful for pharmacol. characterization of peripheral dopamine receptors.