Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Dopexamine hydrochloride is a novel synthetic catecholamine, structurally related to dopamine, with marked intrinsic agonist activity at beta 2-adrenoceptors, lesser agonist activity at dopamine DA1- and DA2-receptors and beta 1-adrenoceptors, and an inhibitory action on the neuronal catecholamine uptake mechanism. The drug is administered by intravenous infusion, and is characterized by a rapid onset and short duration of action. Short term haemodynamic studies in volunteers and patients with severe chronic heart failure have indicated that dopexamine hydrochloride reduces afterload through pronounced arterial vasodilatation, increases renal perfusion by selective renal vasodilation and evokes mild cardiac stimulation through direct and indirect positive inotropism. Preliminary small-scale noncomparative studies indicate that dopexamine hydrochloride displays beneficial haemodynamic effects in patients with acute heart failure and those requiring haemodynamic support following cardiac surgery, and that these effects are substantially maintained during longer term administration (less than or equal to 24 hours). Dopexamine hydrochloride appears to be generally well tolerated. Nausea and vomiting are the most frequently reported adverse effects, and respond to dosage reduction. Occasional reports of chest pain/angina pectoris precipitated by tachycardia indicates the need for caution in the use of dopexamine hydrochloride in patients with ischaemic heart disease. Thus, dopexamine hydrochloride may prove to be a useful alternative to dopamine and dobutamine in the treatment of acute heart failure and the postoperative management of low cardiac output states, although controlled studies are required to establish its efficacy and tolerability with respect to that of established therapies.
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PMID:Dopexamine hydrochloride. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute cardiac insufficiency. 197 Feb 88

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 hydrochloride, a compound under evaluation for the acute treatment of heart failure, was examined in vitro for its ability to prevent neuronal uptake of noradrenaline. 2 Despite possessing only weak beta 1-adrenoceptor agonist activity in paced guinea-pig left atria, dopexamine hydrochloride was only 23 times less potent than isoprenaline in augmenting responses of field-stimulated atrial preparations. 3 This potent effect was not observed in field-stimulated atria depleted of noradrenaline by reserpine and in the presence of cocaine was greatly reduced (1 microM) or abolished (50 microM). 4 Dopexamine hydrochloride (3 microM) potentiated the inotropic effect of exogenous noradrenaline in paced atria, thereby resembling cocaine (10 microM) and dopamine (30 microM), both of which are known inhibitors of Uptake. 5 The sodium-dependent uptake of [3H]-noradrenaline into rabbit brain synaptosomes was prevented by dopexamine hydrochloride (IC50 26 nM) and cocaine (IC50 108 nM), as well as by two other catecholamines used in the treatment of heart failure, dopamine (IC50 270 nM) and dobutamine (IC50 380 nM). 6 The cardiac stimulant effect of dopexamine hydrochloride reported in dogs and in patients with heart failure, may therefore be due in part to potentiation of endogenous catecholamines.
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PMID:Inhibition of Uptake1 by dopexamine hydrochloride in vitro. 289 Mar 92

A clinical development program was initiated to identify the hemodynamic profile of activity of dopexamine hydrochloride. Studies in healthy subjects confirmed the cardiovascular activity of dopexamine hydrochloride and demonstrated its potency. Doses of 0.5 to 8 micrograms/kg/min doubled cardiac output without change in mean blood pressure, although pulse pressure did widen. In patients with stable chronic cardiac failure (mainly New York Heart Association class III), dopexamine hydrochloride (4 micrograms/kg/min) increased stroke volume 47 +/- 9%, cardiac index 64 +/- 10% and heart rate 11.7 +/- 3%. Systemic vascular resistance decreased by 42 +/- 5%. At higher doses, cardiac index increased further, but chronotropic effects became more prominent. Subsequent studies in patients recovering from cardiac surgery and studies of longer duration in patients with chronic congestive heart failure have demonstrated a similar hemodynamic profile that is sustained throughout the infusion. The renal vasodilator effects have been confirmed in both healthy subjects and patients. With all catecholamines the balance of chronotropic to inotropic or vasodilator effect is critical. Dopexamine hydrochloride (1 to 4 micrograms/kg/min) increases cardiac index by over 40% at clinically insignificant (10%) increases of heart rate.
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PMID:Clinical development of dopexamine hydrochloride (Dopacard) and an overview of its hemodynamic effects. 304 60

The short- and long-term hemodynamic effects of intravenous dopexamine hydrochloride (Dopacard) were studied in 12 patients with low cardiac output left ventricular heart failure. In the short-term study, a dose of 4 micrograms/kg/min produced a 60% increase in cardiac output (p less than 0.001), a 30% increase in stroke volume (p less than 0.01), a 23% increase in heart rate (p less than 0.01) and a 39% decrease in systemic vascular resistance (p less than 0.001). In the long-term study, there was a sustained hemodynamic benefit after 8 hours of dopexamine hydrochloride infusion (mean dose 3.5 micrograms/kg/min). There was a 32% increase in cardiac output (p less than 0.001), an 18% increase in stroke volume (p less than 0.05), a 12% increase in heart rate (p less than 0.001) and a 30% decrease in systemic vascular resistance (p less than 0.01). After 48 hours of dopexamine hydrochloride infusion (mean dose 3.8 micrograms/kg/min), the hemodynamic effect was significant only for cardiac output (+20%, p less than 0.05) and for systemic vascular resistance (-26%, p less than 0.01). Thus, dopexamine hydrochloride has beneficial short-term hemodynamic effects in patients with low-output left ventricular heart failure and the benefit appears to diminish with long-term infusion.
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PMID:Use of dopexamine hydrochloride in intensive care patients with low-output left ventricular heart failure. 340 98

Dopexamine hydrochloride is a new synthetic catecholamine for intravenous use in low cardiac output states with co-existing raised systemic or pulmonary vascular resistance. Dopamine has been commonly used since several years in these situations. The drawbacks of dopamine include a vasoconstrictive effect with high infusion rates, and a marked tendency for ventricular ectopy due to the potent beta-1 adrenergic stimulation. Dopexamine hydrochloride has interesting vasodilator properties, with marked intrinsic agonist activity at beta-2 adrenoreceptors and a lesser agonist activity at dopaminergic receptors (DA1 and DA2). Its mild inotropic activity arises primarily from baroreceptor reflex stimulation with a possible contribution from direct stimulation of myocardial beta 2-adrenoreceptors. Dopexamine hydrochloride is responsible for an inhibition of neuronal re-uptake of catecholamines (uptake-1), producing an indirect stimulation of cardiac beta 1-receptors. This catecholamine has no effect at alpha 1 and alpha 2-adrenoreceptors, and only very weak and clinically insignificant beta 1-adrenoreceptor agonist activity. Dopexamine hydrochloride improves cardiac performance by a marked vasodilation and a mild inotropic activity. The specific activity at dopaminergic receptors increases cerebral, myocardial, splanchnic and renal blood flows. These haemodynamic effects are associated with an increase in diuresis and natriuresis. These benefits are achieved without side effects such as an increased myocardial oxygen consumption, although induced tachycardia may be responsible for chest pain/anginae pain in patients with ischaemic heart disease. In clinical practice, dopexamine hydrochloride is easy to use; the short plasma half-life (6 minutes in healthy volunteers and 11 minutes in patients with low cardiac output) allows a rapid return to pretreatment status at discontinuation of the infusion. Preliminary studies have shown that dopexamine hydrochloride can produce beneficial effects in patients with acute heart failure or with compromised left ventricular function following cardiac surgery. The drug has also been assessed in patients with septic shock, most often in association with dopamine or norepinephrine. In these patients, dopexamine produces a dose-related increase in cardiac index, stroke volume, heart rate and a decrease in systemic vascular resistance. Its use in this indication must be cautious, particularly in patients with hypotension or decreased venous return. Comparative therapeutic trials are clearly required to establish the efficiency and tolerance of dopexamine hydrochloride in comparison with dopamine and dobutamine, before its place in therapy can fully be defined.
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PMID:[Dopexamine: a new dopaminergic agonist]. 790 85

Dopexamine hydrochloride, a synthetic dopamine analog with predominantly beta and delta agonist properties, has been shown to improve cardiac performance and renal function in adults with heart failure. This study was designed to investigate the haemodynamic and renal effects of dopexamine in children after cardiac surgery. Seven children were selected in whom a need for postoperative vasodilation after cardiac surgery was anticipated. Haemodynamics and renal function were determined under baseline conditions and during a continuous infusion of dopexamine at 2 and 6 micrograms.kg-1.min-1 for 90 minutes, the sequence being randomized for the initial dose. Cardiac output was measured by thermodilution and glomerular filtration rate (GFR) and renal plasma flow (RPF) by the clearances of inulin and para-aminohippurate respectively. Dopexamine induced a dose-related increase in cardiac index (CI) expressed as mean (SD) from 3.5 (0.7) to 3.9 (0.76) and 4.5 (0.8) l.min.-1m-2 (both P < 0.05), and in heart rate (HR) from 107 (17) to 122 (17) and 136 (17) beats.min-1 (P < 0.05). Stroke volume index (SVI) and mean systemic pressure were unchanged, but pulmonary wedge pressure decreased from 14 (3) to 11 (4) and 12 (3) mmHg (both P < 0.05). Systemic vascular resistances (SVR) decreased from 24 (7) to 20 (5) mmHg.l-1.min-1.m-2 (P < 0.05), with dopexamine 6 micrograms.kg-1.min-1. Renal blood flow (RBF) increased from 319 (113) to 441 (230) and 410 (138) ml.min-1.m-2 (both P < 0.05), GFR from 115 (32) to 142 (34) and 146 (29) ml.min-1.1.73m-2 (both P < 0.05), urine output and fractional excretion of sodium respectively from 3.12 (2) to 7.16 (8) and 7.21 (6) ml.kg-1 (both P < 0.05) and from 2.24 (1) to 4.25 (3.4) (P < 0.05) and 3.15 (3.1)% (n.s.). The fraction of CI delivered to the kidneys, the fraction of RBF filtered in the kidneys, plasma renin activity and aldosterone levels remained unchanged. In children after cardiac surgery, dopexamine increases CI at the expense of a concomitant increase in heart rate and demonstrates few selective vascular systemic or intrinsic renal actions.
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PMID:Haemodynamic and renal effects of dopexamine after cardiac surgery in children. 886 39