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)

In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced, whereas beta-2 adrenoceptor changes vary depending on the etiology of the disease. Beta Adrenoceptor agonists can be used for short-term inotropic support in chronic heart failure; their clinical efficacy might depend on which beta adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta adrenoceptor subtype(s) involved in the positive inotropic effects of clinically used beta adrenoceptor agonists was characterized on isolated electrically driven human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP 20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI 118,551 (30 nmol/l). Epinine evoked positive inotropic effects through stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2 adrenoceptor component. Both agonists were full agonists causing the same maximum increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax = 0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta-1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full agonist, indicating that part of its positive inotropic effect is indirect via the release of endogenous noradrenaline. Xamoterol did not exert positive inotropic effects, but concentration-dependently slightly decreased basal force of contraction.
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PMID:Characterization of the beta adrenoceptor subtype(s) mediating the positive inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in isolated human right atrium. 135 51

Ibopamine is an orally active derivative of dopamine (DA) which metabolizes to its active form, epinine. Epinine is one of the few catecholamines that possess dopaminergic--DA1 and DA2--activity, alpha 1, alpha 2, beta 1, and beta 2 activity, with indirect sympathomimetic action of dopamine. Ibopamine increased positive dP/dt, stroke volume, aortic blood flow, renal blood flow, and diuresis in animals. In healthy volunteers and patients with heart failure, a single oral dose of ibopamine showed primary vasodilating action (postsynaptic DA1 activity and presynaptic DA2 activity). Following a single oral dose of 100 or 200 mg of ibopamine, the plasma concentration of epinine reached its peak within 30 minutes, and declined rapidly so that concentration was not detectable after 1.5-3 hours. Pharmacokinetics and hemodynamic effects in congestive heart failure patients are also discussed.
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PMID:Clinical pharmacology of ibopamine. 167 50

The present study was aimed to characterize the effects of epinine, the metabolite of the p.o. active dopamine derivate ibopamine in human cardiovascular tissues such as myocardium, coronary artery and pulmonary artery. Isometric force of contraction was studied in electrically driven papillary muscle strips from nonfailing (brain death), moderately failing (New York Heart Association class II-III, mitral valve replacement) and terminally failing human myocardium (New York Heart Association class IV, heart transplants) as well as in auricular trabeculae (aortocoronary bypass operation). Epinine increased force development in a concentration-dependent manner. In comparison to isoprenaline, epinine had a significantly lower potency but a similar efficacy to enhance force of contraction. Depending on the degree of myocardial failure, the effectiveness of epinine was reduced, whereas the potency was similar. Only in nonfailing myocardium, epinine increased force of contraction as effectively as Ca++. Prestimulation with forskolin or milrinone enhanced the potency of the epinine-mediated inotropic effect. In contrast, the beta-1-selective antagonist CGP 207.12A [2-hydroxy-5-(2-(hydroxy-3-(4-((1-methyl-4-trifluoromethyl)-1-H-imidazol -2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide] and the beta-2-selective antagonist ICI 118.551 [erythro-(+-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride] shifted the concentration-response curve of epinine significantly to the right, indicating action at both beta-2 and beta-1 adrenoceptors. Epinine exerted higher affinity at beta-2 compared to beta-1 adrenoceptors in radioligand binding experiments ([125I]iodocyanopinodolol). In human coronary artery rings and pulmonary artery rings epinine alone as well as epinine in the presence of propranolol initiated a concentration-dependent increase in tension development in precontracted (prostaglandin F2 alpha, 0.3 mumol/l) as well as in non-precontracted rings. These results suggest that epinine exerts no direct vasodilatory activity in human coronary and pulmonary arteries at concentrations which are capable to produce positive inotropic activity. The supposed beneficial effects of ibopamine in the treatment of heart failure may not be due to positive inotropic actions as the concentrations producing positive inotropy are much higher than the clinically observed plasma concentrations.
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PMID:Cardiac inotropic as well as coronary and pulmonary artery actions of epinine in human isolated tissues. 838 40