Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of a combination of an antioxidant (alpha-tocopherol) and membrane-protective agents (nicotinamide, a lipase inhibitor and delagil, a phospholipase inhibitor) was evaluated in 25 patients with myocardial infarction in the acute period. The drugs were given no later than 8 hours of the onset of the disease within the first 10 days. Along with necrotic area limitation (by 20.2%) and neurotic myocardium was mass decrease by (34.9%), alpha-tocopherol in combination with nicotinamide and delagil was found to lower the frequency and severity of fatal complications, but fail to affect the incidence of relapses of postinfarction angina.
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PMID:[Clinical course and necrotic area size in patients with myocardial infarct receiving combined treatment including antioxidants and membrane-protecting agents]. 182 73

The term "hibernating" myocardium has been applied to chronic left ventricular dysfunction without angina or ischemic electrocardiographic changes in patients with coronary artery disease that is reversed by therapy that increases myocardial blood flow. To investigate the relation between coronary blood flow and ventricular function experimentally, graded reductions in coronary artery pressure were produced in isolated perfused rat hearts as contractile performance (peak systolic pressure and its first derivative [dP/dt]) and metabolic variables were measured using phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy. As coronary pressure and flow were reduced, significant reductions in myocardial oxygen consumption and contractile performance were observed, which returned to control levels when coronary artery pressure and flow were restored to baseline values. Two phases of metabolic abnormality were observed. With modest reductions in coronary perfusion, proportionate reductions in myocardial oxygen consumption and contractile behavior were accompanied by a slight reduction in creatine phosphate but no significant lactate production. With greater reductions in coronary artery pressure and flow, creatine phosphate decreased more, adenosine triphosphate levels and myocardial pH decreased significantly and myocardial lactate production increased. The balanced reductions in myocardial contractility and oxygen consumption without metabolic abnormalities traditionally associated with "ischemia" observed in the first phase provides evidence in normal hearts for resetting of the myocardial contractile behavior and oxygen consumption in the presence of reduced coronary flow (that is, hibernating myocardium). The data suggest that reductions in adenosine diphosphate and the index of the reduced form of nicotinamide adenine dinucleotide (NADH) (lactate formation) do not explain the coupling between coronary artery pressure and flow and myocardial oxygen consumption as contractile performance decreases.
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PMID:Effect of graded reductions of coronary pressure and flow on myocardial metabolism and performance: a model of "hibernating" myocardium. 203 99

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.
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PMID:Pharmacology and therapeutic effects of nicorandil. 215 May 92

Nicorandil, a nicotinamide derivative, is a recently developed, orally active antianginal drug with a cardioprotective activity, and its pharmacologic properties differ from those of conventional antianginal drugs. Nicorandil has the capacity to increase myocardial oxygen supply without increasing oxygen demand by reduction in preload and afterload. In isolated blood-perfused canine heart preparations, when injected into the sinus node, the atrioventricular node or the anterior septal arteries, nicorandil at dose levels doubling blood flow through the respective arteries has virtually no effect on sinus rate, atrioventricular conduction time or contractile force of ventricular muscle. This may indicate that nicorandil possesses a selective effect on the coronary vasculature rather than on the myocardium. Furthermore, the vasospasmolytic activity of nicorandil has been evidenced in in vivo and in vitro experiments. The precise mechanism by which nicorandil develops coronary vasodilating and vasospasmolytic effects remains to be elucidated, but it may be partly inferred by an increase in the potassium conductance in the membrane, a relation with cyclic guanosine monophosphate formation, or inhibition of intracellular calcium ion mobilization in the cell of coronary vascular smooth muscle. Nicorandil possesses a nitrate moiety in its chemical structure. However, it is noted that nicorandil unlike nitrates does not develop tolerance or cross tolerance to other conventional nitrates in terms of blood-pressure lowering effects and coronary vasodilating effects. Thus, nicorandil is likely to have highly beneficial properties in the treatment of angina pectoris.
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PMID:Nicorandil: animal pharmacology. 252 21

This report presents the findings of some studies on single intravenous and oral dosing performed in healthy volunteers to determine the pharmacokinetics and preliminary metabolism of nicorandil, a new vasodilator acting via increase of both membrane potassium conductance and intracellular cyclic guanosine monophosphate in vascular smooth muscle. Nicorandil (5 to 40 mg) is rapidly and completely absorbed after oral administration. Absolute bioavailability is 75 +/- 23% (mean +/- standard deviation) indicating that no significant hepatic first-pass effect exists; peak plasma levels occur within 0.30 to 1.0 hours after dosing. Maximal concentration and area under the plasma concentration time curve of the parent drug are linearly related to a dose range of 5 to 40 mg, which covers the therapeutic regimen proposed for the treatment of patients with angina pectoris. The apparent distribution volume is about 1.4 liters/kg and the plasma concentrations decline according to 2 different processes: (1) a rapid elimination phase (apparent t1/2 beta congruent to 1 hour) that involves about 96% of the dose found in plasma, and a slower phase between the eighth and twenty-fourth hour that could be the consequence of the vascular affinity of the compound. Nicorandil is weakly bound to human plasma proteins (free fraction greater than 75%) and its mean residence time is close to 1.25 hour. Both in animals and in humans, preliminary metabolic studies show that the main biotransformation pathways are denitration and then introduction into the nicotinamide metabolism. However, unchanged nicorandil and denitrated metabolite excreted into the urine represent only about 1 and 4% of the dose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics of nicorandil. 252 22

The effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75, Nicorandil), were examined in an experimental model of angina pectoris, utilizing methacholine-induced ECG changes as main parameter in intact anesthetized rats. The right carotid artery was exposed and through it a special cannula was inserted to a point near the right and left coronary ostium. Such a device made it possible to inject drugs more selectively into the coronary artery. Single intra-aortic injections of 4 to 8 micrograms of methacholine caused a transient elevation of the ST segment and T wave of the electrocardiogram (ECG). SG-75 (3 mg/kg i.v. or 10 mg/kg p.o.) prevented these changes in the ECG, while a potent vasodilator, papaverine, failed to do so. In the isolated, donor-perfused rat heart, SG-75 (1-30 micrograms) injected into the coronary perfusion system caused dose-dependent vasodilation, while 0.1-0.8 micrograms acetylcholine as well as methacholine produced marked vasoconstriction. SG-75 (10 mg/kg) administered orally to the donor rat inhibited the coronary vasoconstriction produced by the cholinomimetic drugs, whereas papaverine (30 micrograms i.a.) failed to prevent it. The inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats seemed to be due to its spasmolytic action.
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PMID:Effects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ECG changes in intact anesthetized rats. 645 23

The effect of N-(2-hydroxyethyl)-nicotinamide nitrate ester (nicorandil) on rat heart monoamine oxidase (MAO) was investigated in vitro. MAO activity was assayed by the isotopic method with 14C-tryptamine as substrate. Nicorandil significantly inhibited MAO activity of rat heart mitochondria. The effect of nicorandil on the enzymatic kinetics of MAO of rat heart mitochondria indicates that the anti-anginal drug acts as a competitive inhibitor of MAO. The inhibitor constant (Ki) of nicorandil was 4.93 mmol/l. The Ki of nicorandil was fitted to the formula derived from the relationship between the Ki values of glyceryl trinitrate, erythrytol tetranitrate, mannitol hexanitrate and isosorbide dinitrate and the dose of these drugs recommended to relieve anginal pain in patients. The dose of nicorandil was 0.071 mmol (15.0 mg at a time). This value agreed with the clinical dose for patients (10--20 mg at a time).
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PMID:The dose of nicorandil in men predicted from the inhibition of MAO activity by organic nitrates. 645 97

The nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is a major source of superoxide anion (.O2-) production in the human vasculature and may therefore influence lipid peroxidation and severity of atherosclerosis. This study aimed to investigate a hypothetical influence of the p22 phox C242T polymorphism on the generation of malondialdehyde (MDA), extent and clinical onset of coronary artery disease (CAD) in patients. We studied 108 male Caucasians with angiographically documented CAD and 45 controls free of vascular disease under 60 years of age. p22 phox C242T genotypes and MDA levels were determined. Additional information was obtained from each subject on classic risk factors and clinical events of CAD. Genotype distribution in CAD-patients and controls was thymine-thymine (TT): 13.8% (13.3%), cytosine-thymine (CT): 46.3% (53.3%) and cytosine-cytosine (CC): 39.8% (33.3%), respectively. No significant influence was seen of the p22 phox C242T polymorphism on corresponding mean MDA levels in both groups. Furthermore, age at onset of first time angina pectoris (AP) and myocardial infarction (MCI) was not significantly different between genotype groups. It is concluded that the C242T polymorphism of the p22 phox gene is not associated with lipid peroxidation as measured by MDA, and is not a genetic risk marker for CAD Caucasians.
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PMID:NADH/NADPH oxidase p22 phox C242T polymorphism and lipid peroxidation in coronary artery disease. 1172 80

The incidence of ischaemic heart disease and acute myocardial infarction are greater in people with diabetes than in nondiabetic individuals. Heart disease patients with diabetes have a higher incidence of mortality during and following an acute myocardial infarction and a high risk for progression to heart failure post-infarction. The greater occurrence of ischaemic heart disease is partially due to a poorer coronary artery disease risk factor profile in diabetic patients, and, importantly, due to diabetes-induced abnormalities in the myocardium, termed 'diabetic cardiomyopathy'. The main metabolic abnormalities in the diabetic myocardium are impaired carbohydrate metabolism, specifically reduced pyruvate oxidation in the mitochondria and a greater reliance on fatty acids and ketone bodies as fuels. The healthy heart takes up glucose and lactate and converts them to pyruvate; however, in the diabetic heart there is a reduced capacity to oxidize pyruvate, and thus less glucose and lactate uptake. The defective metabolism is due to high circulating free fatty acids and ketone body concentrations in the plasma, resulting in greater acetyl-Co-enzyme A/Co-enzyme A and reduced nicotinamide adenonine dinucleotide/nicotinamide adenonine dinucleotide+ ratios in the mitochondria, and the subsequent inhibition of pyruvate dehydrogenase. Pharmacological inhibition of fatty acid oxidation during ischaemia increases myocardial pyruvate oxidation and provides clinical benefit to patients with stable angina or ischaemic left ventricular dysfunction. Recent clinical trials with trimetazidine, an inhibitor of the fatty acid beta-oxidation enzyme long chain 3-ketoacylthiolase, showed improvement in cardiac function and exercise performance in diabetic patients with ischaemic heart disease, illustrating the effectiveness of this approach in diabetes.
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PMID:Rationale for a metabolic approach in diabetic coronary patients. 1634 Mar 98

We report the unusual complication of penile ulceration caused by Nicorandil, a nicotinamide ester used in the treatment of symptomatic angina pectoris.
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PMID:Nicorandil induced penile ulceration. 2237 86


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