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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation. 136 32

This review discusses the localization of adrenergic- and dopaminergic-adrenoceptors within the cardiovascular system and describes the cardiovascular and renal changes produced following the activation of these receptors by appropriate agonists. Whereas the role of alpha- and beta-adrenergic agents in the treatment of heart failure is well recognized, recent studies with dopamine (DA)-receptor agonists indicate that they offer a novel approach in the therapy of congestive heart failure. DA-adrenoceptor agonists reduce afterload by causing vasodilation and promote sodium excretion via direct activation of DA1-adrenoceptors located on renal tubules. Fenoldopam is a selective DA1-adrenoceptor agonist found to be effective in heart failure. It reduces afterload by causing peripheral vasodilation and produces natriuresis and diuresis. Dopexamine is a DA1- and beta 2-adrenoceptor agonist, and its efficacy in heart failure is due to its ability to provide mild inotropic support and cause a reduction in afterload. Ibopamine is a prodrug that is converted into its active metabolite, epinine. This compound activates primarily DA1- and DA2-adrenoceptors. It is effective in heart failure, and the mechanism progresses via DA1- and DA2-adrenoceptor-mediated reduction in afterload. Agonists of DA2-adrenoceptors reduce afterload by decreasing the release of norepinephrine and by reducing the levels of renin-angiotensin-aldosterone system. Since both of these systems are active in heart failure, ibopamine offers a rational approach for therapy. The present review addresses the concept of pharmacologic intervention in adrenergic and dopaminergic influence in the cardiovascular and renal systems to produce changes that are desirable for the pharmacotherapy of congestive heart failure.
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PMID:Cardiovascular pharmacology of adrenergic and dopaminergic receptors: therapeutic significance in congestive heart failure. 167 49

Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure.
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PMID:Comparison of the haemodynamic effects of dopexamine and dobutamine in patients with severe congestive heart failure. 201 Feb 43

1. Dopexamine is a novel analogue of dopamine which is free of alpha-adrenoceptor activity and is of therapeutic value in chronic heart failure. The effects of dopexamine on the in vitro function of platelets from 10 healthy subjects at rest, after exercise and after in vitro addition of adrenaline and noradrenaline were investigated. 2. Dopexamine in a wide range of concentrations (10(-9)M-10(-3)M) did not appear to function as an agonist on platelets either in whole blood or in PRP preparations. 3. Dopexamine caused a dose-dependent inhibition of agonist-induced platelet aggregation in both whole blood and PRP. The inhibitory effect of dopexamine was significantly greater in PRP than in whole blood, and significantly greater to adrenaline than to collagen or ADP as agonists in whole blood. 4. After exercise or after in vitro addition of adrenaline and noradrenaline at concentrations commonly seen in myocardial infarction, dopexamine produced similar levels of inhibition seen with platelets from resting subjects. 5. Dopexamine did not affect plasma catecholamine levels but caused an increase in intraplatelet noradrenaline levels. 6. This study suggests that dopexamine is unlikely adversely to affect the hyperaggregable state found in patients with cardiogenic shock after myocardial infarction.
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PMID:The effects of dopexamine, a new dopamine analogue, on platelet function in stress. 239 Apr 35

Dopexamine (FPL 60278) is a new vasodilator possessing both postjunctional dopaminergic and beta 2-adrenoceptor agonist actions. Its acute haemodynamic effects were compared in a cross-over study with those of dobutamine, captopril, and glyceryl trinitrate (GTN) in eight adult patients with chronic heart failure. Dopexamine, 1 microgram/kg/min intravenously (i.v.) for 10 min, increased cardiac index, systolic blood pressure, and heart rate while reducing systemic vascular resistance. Pulmonary artery end-diastolic pressure was unchanged. Plasma norepinephrine (NE) increased during dopexamine infusion. No arrhythmias occurred. Dobutamine, 5 micrograms/kg/min i.v. for 10 min, increased cardiac index and systolic blood pressure similarly but did not increase heart rate or reduce vascular resistance. Captopril, 25 mg orally, did not alter cardiac index at 1 h, but reduced heart rate, blood pressure, pulmonary diastolic pressure, and vascular resistance. GTN, 100 micrograms sublingually, reduced pulmonary diastolic pressure but did not affect other variables at 5 min. Dopexamine, because it combines some of the properties of dopamine and salbutamol, may have a role in the management of severe low output cardiac failure.
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PMID:Acute hemodynamic and neuroendocrine effects of dopexamine, a new vasodilator for the treatment of heart failure: comparison with dobutamine, captopril, and nitrate. 243 36

Dopexamine is a novel compound that has DA1-dopaminergic and beta 2-adrenergic agonist properties capable of producing beneficial systemic and renal vasodilation. The acute haemodynamic effects in 10 patients with low-output-state ischaemic cardiac failure (NYHA IV) were recorded before (control) and during graded incremental doses of dopexamine infusion from 0.5 to 6.0 micrograms/kg/min. Dopexamine produced a marked increase in cardiac index from 1.6 +/- 0.2 (control) to a maximum of 2.8 +/- 0.4 L/min/m2 (p less than 0.001) primarily by inducing vasodilation, with reduction in systemic vascular resistance from 1,720 +/- 136 (control) to 1,116 +/- 136 dynes.s.cm-5 (p less than 0.05). Using a more sophisticated analytical technique which enables us to separate direct inotropic from vasodilatory effects, we were able to identify, in eight of the patients, a direct dopexamine-induced positive inotropism. These beneficial central haemodynamic effects of dopexamine, when coupled with its known DA1-dopaminergic agonist property, indicate that dopexamine may have a place in the management of patients in severe heart failure.
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PMID:Beneficial haemodynamic effects of intravenous dopexamine in patients with low-output heart failure. 244 75

The results of the present study show that the reduction of the total number of beta adrenoceptors affected the beta 1-adrenoceptor subpopulation, whereas the beta 2 adrenoceptors were not detectably altered in the failing heart. Dopexamine had a 9.8-fold greater affinity to beta 2 adrenoceptors than to beta 1 adrenoceptors. In nonfailing myocardium, dopexamine increased force of contraction concentration-dependently. However, dopexamine alone had no effect in papillary muscle strips from moderately (NYHA II-III) and severely (NYHA IV) failing myocardium. However, in the presence of milrinone, it concentration-dependently increased force of contraction. Under this condition, the effectiveness was slightly less pronounced in NYHA IV than in NYHA II-III. Dopexamine concentration-dependently stimulated adenylate cyclase activity. Experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist ICI 118.551 showed that both stimulation of adenylate cyclase and the increase of force of contraction are mediated by beta 2 adrenoceptors. It is concluded that although the number of beta 2 adrenoceptors is preserved in the failing myocardium, dopexamine alone does not increase force of contraction. However, the positive inotropic effect of dopexamine, which is observed in the presence of milrinone and the stimulation of adenylate cyclase activity by dopexamine are mediated by beta 2 adrenoceptors. Therefore, beta 2 adrenoceptors exist in the human myocardium, are coupled to adenylate cyclase, and are capable of increasing force of contraction. These results provide evidence for an impaired coupling of beta 2 adrenoceptors to mechanisms beyond receptor occupation in terminal heart failure.
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PMID:Reduced effects of dopexamine on force of contraction in the failing human heart despite preserved beta 2-adrenoceptor subpopulation. 247 68

Dopexamine is an agonist at peripheral dopamine receptors and at beta 2-adrenoceptors. Dopexamine has approximately one-third the potency of dopamine in stimulating the vascular DA1-receptor in the dog, resulting in a fall in renal vascular resistance of 20% at 2.3 X 10(-8) mol kg-1 (i.a.). Prejunctional DA2-receptors are also stimulated by dopexamine, resulting in a reduction of neurogenic vasoconstriction in the rabbit isolated ear artery (IC50 of 1.15 X 10(-6)M) and of neurogenic tachycardia in the cat (ID50 of 5.4 X 10(-8) mol kg-1, i.v.), with a potency six and four times less respectively than that of dopamine. By contrast, dopexamine is approximately 60 times more potent than dopamine as an agonist at the beta 2-adrenoceptor of the guinea-pig isolated tracheal chain, with an EC50 of 1.5 X 10(-6)M. Both dopexamine and dopamine are weak agonists at the guinea-pig atrial beta 1-adrenoceptor over the concentration range 10(-7) to 10(-4) M, but dopexamine has an intrinsic activity of only 0.16 relative to dopamine. Dopexamine does not stimulate postjunctional alpha 1- or alpha 2-adrenoceptors in the canine isolated saphenous vein, whereas dopamine is an agonist, approximately 120 times less potent than noradrenaline. Unlike dopamine and salbutamol, dopexamine does not cause arrhythmias in the guinea-pig isolated perfused heart at doses of up to 10(-5) mol, which is a thousand times the minimum cardiostimulant dose. The combination of agonist properties at peripheral dopamine receptors and at beta 2-adrenoceptors, with little or no activity at alpha- and beta 1-adrenoceptors gives dopexamine a novel pharmacological profile. This may confer advantages over dopamine in the treatment of acute heart failure.
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PMID:Dopexamine: a novel agonist at peripheral dopamine receptors and beta 2-adrenoceptors. 286 44

Dopexamine increases inotropic state and rate of relaxation independent of changes in heart rate. Dopexamine has a chronotropic effect and results in a decrease in systemic vascular resistance. Dopexamine has a spectrum of action that should be useful in patients with severe heart failure.
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PMID:The haemodynamic and myocardial effects of dopexamine: a new beta 2-adrenoceptor and dopaminergic agonist. 287 52

Dopexamine is a new vasodilator with a combination of dopamine receptor and beta 2 adrenoreceptor agonist properties. Its haemodynamic effects were assessed after dose titration and during infusion for up to 24 hours in 15 patients with heart failure after acute myocardial infarction. At the initial titration a dose of 1 micrograms/kg/min produced a 25% decrease in the systemic vascular resistance index and a 32% increase in cardiac index. Stroke volume index and heart rate increased by 23% and 9% respectively. Left ventricular filling pressures and mean blood pressures were not affected. The short term effects were well sustained during the long term infusion and tolerance did not develop. Administration of dopexamine to patients with heart failure after acute myocardial infarction augments cardiac performance at rest.
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PMID:Haemodynamic response to dopexamine hydrochloride in postinfarction heart failure: lack of tolerance after continuous infusion. 322 52


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