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 present study was carried out to investigate exercise test results and the outcome of the quality of life after administration of trapidil (CAS 15421-84-8, Rocornal) or nifedipine (CAS 21829-25-4) to patients with coronary heart disease. The characteristics of the life quality in combination with the results of exercise test are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacological approach in individual patients. In this prospective multicentre study, 144 patients with stable angina were enrolled in 6 centres. Due to protocol violations and drop-outs 116 patients were evaluated for tolerability; 101 patients were evaluated for efficacy. After baseline evaluation, consisting of an exercise test and a questioning investigating patients' anginal symptoms and several psychometric testings, the patients were randomly allocated to double-blind treatment for 12 weeks with either trapidil, 200 mg t.i.d. or nifedipine, 10 mg t.i.d. according to a parallel group design. After 6 and 12 weeks exercise tests and psychometric testings were repeated. Both trapidil and nifedipine prolonged exercise tolerance (trapidil 39.2% vs. nifedipine 33.3%) or increased the total exercise over baseline levels (trapidil 57.8% vs. nifedipine 61.2%). Using Mann-Whitney U-test the SB-S-rating scale and the physician's assessment revealed a comparable improvement of life quality (trapidil 69.4% vs. nifedipine 80.0%) under both treatments. In addition patient questioning showed a significant reduction in angina attacks and in nitroglycerin consumption. None of the characteristics of anginal symptoms or exercise test gave evidence for a significant difference between nifedipine and trapidil. Both drugs demonstrated similar safety profiles (adverse events (AEs) 12.7% for trapidil and 11.1% for nifedipine); four patients of the trapidil group and one of the nifedipine group discontinued the clinical trial because of AEs. The results of a baseline exercise test and rating questionnaires may offer useful information for selecting medical treatment in stable angina pectoris.
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PMID:[The effects of treatment with trapidil compared to nifedipine on physical, emotional and cognitive exercise tolerance in patients with coronary heart disease]. 896 5

Nitroglycerin (glyceryl trinitrate, CAS 55-63-0, NTG) administered with an oral spray may be more effective in relieving anginal pain than sublingual tablets especially when the patient's mouth is dry. In this study, the effect of a NTG oral spray (Myocor Spray) on exercise-induced angina was compared with that of a sublingual tablet in relation to the oral dryness. In 17 patients with effort angina, graded bicycle exercise was performed twice at an interval of one week. Exercise was discontinued upon the onset of moderate anginal pain. Immediately after exercise, the oral dryness was evaluated by touching the tip of the tongue with a blotting paper for a moment. Then, 0.3 mg of NTG was administered by either a squirt of spray or a sublingual tablet in a randomized crossover fashion. Exercise results were reproducible between two exercise tests. According to the extent of the wet area of the blotting paper, the subjects were divided into two groups. In 7 patients of the wet group, the remission times of chest pain and ST segment depression were not significantly different by the formulation of NTG. In 10 patients of the dry group, however, both chest pain and ST depression more rapidly recovered with use of the oral spray (p < 0.05 and p < 0.05, respectively). These results strongly suggest that the NTG oral spray is superior to the sublingual tablet in relieving anginal attacks, when the oral wetness is decreased.
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PMID:Studies on the response of nitroglycerin oral spray compared with sublingual tablets for angina pectoris patients with dry mouth. A multicenter trial. 907 31

The pharmacokinetics of a new sustained release tablet (40 mg, "test") of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) was investigated together with a reference preparation (20 mg, "reference") after single and multiple oral administration in ten healthy human subjects using an open, randomised two-way crossover experimental design. Based on the statistical evaluation of the area under the plasma concentration-time curve (AUC), the two tablet formulations are judged to be the same with regard to the amount absorbed. Pharmacokinetic data showed that with the test tablet significantly lower and delayed mean peak plasma levels (Cmax) were reached compared with the reference preparation in both single and multiple dose studies. The test formulation also produced lower minimum plasma concentration (Cmin). However, there was no statistically significant difference for other pharmacokinetic parameters, including the elimination rate constant (Kel), the elimination half-life (t1/2) and the peak-trough fluctuation constant (PTF) between the two treatments. It was demonstrated that the new sustained release formulation of isosorbide-5-mononitrate could be useful in clinical practice for the treatment of angina pectoris and congestive heart failure.
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PMID:Single and multiple dose pharmacokinetic studies of oral sustained release and non-sustained release formulations of isosorbide-5-mononitrate in healthy volunteers. 968 20

The effects of ranolazine (CAS 95635-55-5, KEG-1295), a novel antianginal drug, on the ST-segment changes induced by coronary ligation, epinephrine, and vasopressin were examined following oral or intraduodenal administration. In anesthetized dogs, intraduodenal administration of KEG-1295 (10, 30, or 50 mg/kg) or atenolol (10 mg/kg) significantly attenuated the ST-T wave elevation induced by 2-min coronary ligation imposed during electrical heart pacing (200 beats/min). This antianginal effect of KEG-1295 persisted for 3 h without any changes in hemodynamic parameters, while that of atenolol was accompanied by more or less maintained decreases in diastolic blood pressure, heart rate, and the maximum first derivative of left ventricular pressure. In anesthetized rats, oral administration of KEG-1295 (10, 30, or 50 mg/kg) attenuated the ST-T wave elevation induced by epinephrine (0.3 microgram/kg i.v.) in a dose-dependent manner, although KEG-1295 (10 or 30 mg/kg p.o.) failed to attenuate the ST-segment depression induced by vasopressin (0.2 IU/kg i.v.). These findings suggest that, taken orally, KEG-1295 may exert potent protective effects against angina pectoris, except that caused by vasospasm. Further, KEG-1295 may be categorized as a new type of antianginal agent, without any primary hemodynamic effects.
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PMID:Antianginal effects of ranolazine in various experimental models of angina. 1021 61

The vascular effects of JTV-506 ((-)-(3S,4R)-2.2-bis(methoxymethyl)- 4-[(1,6-dihydro-l-methyl-6-oxo-3-pyridazinyl)amino]-3-hydroxychroman+ ++-6- carbonitrile hemihydrate, CAS 170148-29-5), a new potassium channel opener, was evaluated in isolated coronary arteries and anesthetized dogs. JTV-506 (1 nmol/l-3 mumol/l) produced a concentration-dependent relaxation in porcine isolated epicardial large coronary arteries precontracted with KCl (30 mmol/l), phenylephrine (3 mumol/l), histamine (3 mumol/l), serotonin (5-HT; 300 nmol/l), prostaglandin F2 alpha (PGF2 alpha; 10 mumol/l), U-46619 (100 nmol/l), endothelin-1 (ET-1; 30 nmol/l) and Bay K-8644 (100 nmol/l). JTV-506 was 2.5-8.5 and 13.3-81.5 times more potent than levcromakalim (CAS 94535-50-9) and nicorandil (CAS 65141-46-0), respectively, but was less potent than nifedipine (CAS 21829-25-4). JTV-506 and levcromakalim produced almost a complete relaxation in arteries precontracted with various kinds of vasoconstrictor, except for KCl. In contrast, nifedipine produced about 80-90% relaxation in arteries, precontracted with PGF2 alpha, U-46619 and ET-1. Thus, this potassium channel opener can be characterized as an agonist-nonselective vasorelaxant. The relaxing effects of JTV-506 and levcromakalim on coronary arteries precontracted with 30 mmol/l KCl was competitively antagonized by 3 mumol/l glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. In canine isolated epicardial large coronary arteries, 10 mumol/l JTV-506, 10 mumol/l levcromakalim, 100 mumol/l nicorandil and 0.1 mumol/l nifedipine eliminated 10 mmol/l 3,4-diaminopyridine-induced rhythmic contractions. In anesthetized dogs, when administered directly into the coronary artery, JTV-506 induced dose-dependent increases in coronary arterial diameter and coronary blood flow. These results suggest that JTV-506 elicits coronary vasorelaxation through activation of the KATP channel. It is expected that JTV-506 might be useful in the treatment of coronary vasospasm in angina pectoris.
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PMID:Effects of the new potassium channel opener JTV-506 on coronary vessels in vitro and in vivo. 1021 62

Nitroglycerin (CAS 55-63-0, Nitrocene) has successfully been used in the management of angina during the last several decades. Although important information on the pharmacological actions and efficacy of nitroglycerin have been extracted, to date, limited research has been conducted on its effects on cerebral blood flow. In recent years, with the aid of SPECT (single photon emission computed tomography) and PET (positron emission tomography) it has been shown that marked cerebral blood flow changes occur under treatment of a wide variet of drugs. Illucidation of the pharmacological mode of action of nitroglycerin has gained momentum with the discovery of nitric oxide (NO) as an endogenous mediator and with the knowledge that nitroglycerin acts as a NO donor. The present study investigated the effects of nitroglycerin (0.25 microgram/kg/min over 10 min) on the cerebral blood flow, using 99mTc-HMPAO (hexamethylpropylene amine oxime) and SPECT, in an anaesthetised primate model, as well as the effects of its drug interactions with therapeutic agents that influence cerebrovascular dynamics, e.g. sumatriptan, nimodipine and acetazolamide. The present study with nitroglycerin indicates that the response time to measure cerebral blood flow effects seems to be present and an important factor as the transient is relatively short. The current treatment regime with nitroglycerin indicates a slight increase, when compared with control control results, although not significant, except for regional significant increases in particular the occipital regions of the brain. Drug interaction between nitroglycerin and nimodipine may occur as a reduction of 20% in cerebral blood flow from the control control was observed in this case. The results for the combination of nitroglycerin with sumatriptan showed a further increase of the cerebral blood flow to near significance, when compared with the control results and is significantly increased (+27%) when compared with sumatriptan treatment alone. Effective treatment with sumatriptan may therefore be compromised with simultaneous administration of nitroglycerin or NO donor drugs. The combination of nitroglycerin and acetazolamide suggested that the increase in cerebral blood flow is primarily attributed to the influence of acetazolamide. The cerebral blood flow effects of these drugs and possible interactions during an angina attack need to be investigated.
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PMID:Cerebral blood flow effects of the nitric oxide donor, nitroglycerin and its drug combinations in the non-human primate model. 1051 99

The effects of JTV-506 ((-)-(3S,4R)-2,2-bis(methoxymethyl)-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)amino]-3-hydroxychroman-6-carbonitrile hemihydrate, CAS 170148-29-5), a novel coronary vasodilator, on hemodynamics, cardiac function and cardiac oxygen consumption were evaluated in anesthetized dogs. In anesthetized, open-chest dogs, JTV-506 (0.3-10 micrograms/kg i.v.) induced a marked increase in coronary blood flow in a dose dependent manner, while at these doses it had smaller effects on vertebral and mesenteric blood flow and almost no effect on renal blood flow. JTV-506 (1-10 micrograms/kg i.v.) showed a tendency to decrease oxygen consumption of the heart and elevate myocardial oxygen pressure without cardiac suppression. Effects of JTV-506 on hemodynamics and the respiratory system following i.v. administration (0.3-300 micrograms/kg) were investigated in spontaneously breathing anesthetized dogs. The effective dose to induce hemodynamic changes was more than 3 micrograms/kg. JTV-506 did not have a crucial influence on electrocardiogram. JTV-506 caused marked increase in coronary blood flow and myocardial oxygen pressure with slight change in blood pressure. It is concluded that JTV-506 is a potent vasodilator, with particularly pronounced effect on vasculature of the heart. These results suggest that JTV-506 may be useful in the treatment of angina pectoris.
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PMID:Cardiovascular pharmacological studies on JTV-506, a new potassium channel opener. 1st communication: effects on myocardium and vasculature. 1075 74

The pharmaceutical development and characteristics of the new glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch Epinitril, hereinafter called EPI, are described. EPI is a thin (0.096 mm), transparent patch, with GTN uniformly dissolved in a monolayer pressure-sensitive acrylates vinyl acetate copolymer adhesive matrix. The patch provides an intense flux rate of GTN through the skin (33 micrograms/cm2/h). This is the result of the high concentration of GTN in the matrix (39.3% w/w) and of its thinness (0.033 mm), which elicit a high thermodynamic activity of GTN on the surface of the skin, promoting its absorption. EPI was developed in three strengths with release rates of 5, 10 and 15 mg GTN in 24 h, to allow the adaptation of the dose to the needs of the individual patient. During development, different tests were used to evaluate in vitro the release of GTN, i.e. a) the disk assembly dissolution test, b) the artificial membrane-controlled dissolution test and c) the diffusion test through the stratum corneum and epidermis of human skin. None was able to provide a reliable in vitro-in vivo correlation of the performance of the investigated patches. The tests, however, are useful to evaluate the effects of formulation changes during pharmaceutical development. For its small size, thinness, flexibility, transparency, easiness of application and of removal and for its good tolerability, EPI is very patient friendly, a quality that improves the compliance with the long-term therapeutic courses needed in angina pectoris.
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PMID:Pharmaceutical development and characteristics of a new glyceryl trinitrate transdermal patch 1110 31

The transformation of isosorbide-5-mononitrate (CAS 16051-77-7, IS-5-MN) to the corresponding keto derivative and its ketoxime (oxime-nitrate derivative of isosorbide) is described. The effects of IS-5-MN and the new oxime-nitrate (ON) on the endothelial and smooth muscle cells of isolated rings of the rat superior mesenteric artery were examined. After contraction induced by phenylephrine, IS-5-MN (10(-8)-10(-4) mol/l) caused a concentration-dependent relaxation. Removal of the vascular endothelium strongly potentiated this effect. On the other hand, the new ON (10(-8)-10(-4) mol/l) was a more potent relaxant than the parent drug, but its effect was not dependent on the vascular endothelium. The inhibitory effect of the artery without endothelium to the new ON was more pronounced than that to IS-5-MN. The mechanism of the relaxant effect of the new compound consisted in the liberation of nitric-oxide (NO) which activated guanylate cyclase (GC), upon which accumulation of cyclic guanosine monophosphate (cGMP) occurred, which was the second messenger leading to relaxation. Tolerance to the frequent applications of the new compound was not observed, moreover a slight increase of the effect was detected in comparison with IS-5-MN for which tolerance was observed to a great extent. Clinically, the new ON could be favorable in all types of angina in comparison with the classical IS-5-MN.
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PMID:Comparison of the relaxant effects of a new oxime-nitrate derived from isosorbide-5-mononitrate and the parent drug. 1514 31

Eighteen Chinese male subjects completed a single-blind, randomized, three-treatment, three-period, cross-over study. In each treatment phase, subjects received a single dose of 20 mg isosorbide dinitrate (CAS 87-33-2, ISDN) intravenous infusion, 20 mg isosorbide 5-mononitrate (CAS 16051-77-7, 5-ISMN) tablet or 20 mg isosorbide 5-mononitrate intravenous infusion. Each consecutive dosing was separated by a washout period of 7 days. Following each dosing, venous blood samples were collected over a period of 16 h. Plasma concentrations of ISDN and its two active metabolites isosorbide 2-mononitrate (2-ISMN), 5-ISMN had been measured by a validated gas chromatographic method. Various pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, tmax, t1/2, Kelm and MRT were determined for the three formulations and found to be in good agreement with literature values. AUC0-t and AUC0-infinity of 5-ISMN tablet and intravenous infusion were 2694 +/- 496 ng x ml(-1) x h vs. 2548 +/- 556 ng x ml(-1) x h and 3266 +/- 624 ng x ml(-1) x h vs. 3178 +/- 769 ng x ml(-1) x h, respectively, and the relative bioavailability of 5-ISMN tablet was 105 +/- 20%. As compared with 5-ISMN intravenous infusion, ISDN can rapidly reach the plateau concentration and metabolize to its active metabolites 5-ISMN and 2-ISMN, which both have vasodilator effect. The results of this study suggest that as evaluated from the pharmacokinetic profiles of the three formulations, 5-ISMN tablet and ISDN intravenous infusion are ideal vasodilators and anti-angina drugs especially in acute conditions due to their rapid onset and long duration of action.
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PMID:Pharmacokinetics of three organic nitrates in Chinese healthy male volunteers. 1514 32


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