Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Whether the vasodepressor effects of cromakalim and nicorandil, potassium channel openers, were differentially antagonized by glibenclamide, a supposed specific antagonist of potassium channel openers, was investigated in spinally-anaesthetized dogs in which arterial pressure was maintained elevated by i.v. infusion of noradrenaline. 2. Cumulative administration of cromakalim (3-100 micrograms kg-1, i.v.), nicorandil (30-1000 micrograms kg-1, i.v.), diltiazem (3-300 micrograms kg-1, i.v.) and nitroglycerin (0.3-100 micrograms kg-1, i.v.) caused dose-dependent decreases in mean arterial pressure. In dogs which received glibenclamide (3 mg kg-1, i.v.), the dose-vasodepressor response curves for cromakalim and nicorandil were located on the right in parallel to the respective curves determined in control dogs, but those for diltiazem and nitroglycerin were not different. ED50% values increased about 6.7 fold for cromakalim and 2.2 fold for nicorandil. 3. The depression of LV dP/dtmax produced by a high dose of cromakalim (100 micrograms kg-1, i.v.) was abolished by glibenclamide and that produced by nicorandil was not only antagonized but converted to an increase. 4. These results suggest that the vasodepressor action of cromakalim is due predominantly to potassium channel opening, but that of nicorandil involves not only potassium channel opening but its action as a nitrate.
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PMID:Specific but differential antagonism by glibenclamide of the vasodepressor effects of cromakalim and nicorandil in spinally-anaesthetized dogs. 214 56

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

In summary, these findings indicate the importance of designing future experiments that delineate between opioid and nonopioid forms of respiratory disease and dysfunction, and the need to identify means of diagnosing them in order to achieve successful recovery. Apparently there is great diversity between animal species in terms of contributions of endogenous opioids to tonic control of ventilation, and future work should strive to identify which species is most appropriate as a model of human ventilatory control and disease. Certain opioid receptor types appear to be linked to independent respiratory functions. For instance, mu receptors in the brain stem produce strong inhibitory actions on respiratory parameters, including RR, VT, VE, and CO2 sensitivity. These effects have been observed in vivo and by electrophysiologic recordings in vitro. Delta receptors may also exert some inhibitory effect on respiration, especially in the NTS. In the CNS, the ventral surfaces of the medulla and pons, especially the NTS and NA, seem to be important sites for opioid-induced inhibition of respiration, whereas the spinal cord probably is not involved in opioid-mediated ventilatory depression. Kappa receptors appear to be devoid of respiratory depressant activity, whereas sigma receptors may stimulate some ventilatory parameters. Morphine and similar pure mu agonists, such as fentanyl and oxymorphine, probably produce their analgesic and respiratory depressant effects through stimulation of mu receptors. Mixed agonists/antagonists that have mu antagonist (or partial agonist) activity plus kappa agonist and/or sigma agonist activity show a ceiling effect for respiratory depression. Future tests need to determine which opioid receptor may be responsible for the ceiling effect. In addition, the effects of mu, delta, kappa, and sigma selective agonists on hypoxic drive should also be determined, as a drug that stimulates hypoxic sensitivity in the face of hypercapnic depression may produce less overall respiratory depression due to counteractive effects. In the future, clinically optimal opiates should have more specificity of action than those available now. This may be achieved by creating drugs selective for single receptors or by creating drugs with desirable combinations of receptor selectivities. The combinations of mixed agonists/antagonists with pure mu agonists currently in use today are promising, as they provide analgesia with reduced respiratory depression. In the early days of opiate research and development, combination drug regimens were thoroughly tested to determine the "ideal ratios" that would retain analgesic properties but not the other undesirable effects such as respiratory depression (196).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. 217 88

In a double blind crossed ten-week study with a randomized beginning the authors compared in 25 patients with chronic stable angina pectoris (II-III according to NYHA classification) and with normal blood pressure the effect of placebo, nifedipine, diltiazem and in 16 of the patients (who completed treatment with the combined drugs) also a combination of nifedipine and diltiazem. Nifedipine, 60 mg per day, and diltiazem, 270 mg per day, improved significantly the total amount of performed work as compared with placebo, they delayed significantly the onset of stenocardias and reduced the ST depression in lead V5 during ergometry, they reduced significantly the rate of stenocardias per day as well as the nitroglycerin consumption. Diltiazem, as compared with nifedipine, increased significantly the total volume of performed work and delayed the development of stenocardias during ergometry, the symptomatic improvement of the patients being similar. A combination of 30 mg nifedipine per day with 180 mg diltiazem per day did not lead to improvement, as compared with a higher dose of diltiazem alone, as compared with a higher dose of diltiazem alone. A combination of 60 mg nifedipine per day with 270 mg diltiazem per day did not improve the exercise tolerance, as compared with diltiazem alone, however, it reduced significantly the rate of stenocardias. However, the combination of the latter amounts was tolerated without side-effects only by 13% of the patients (2 of 15 patients), 53% (8 of 15 patients) terminated treatment prematurely because of several side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness of nifedipine, diltiazem and their combination in the treatment of chronic stable angina pectoris]. 220 31

To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20 patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2-4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P less than 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P less than 0.01) and maximal ST change was reduced (P less than 0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 +/- 1.5, felodipine 7.4 +/- 2.0, placebo 6.6 +/- 1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Felodipine in chronic stable angina: a randomized, double-blind, placebo-controlled, crossover study. 228 20

Two case histories are presented. Patient 1 was an agricultural worker, aged 63 years, whose attacks of chest pain, diagnosed as effort angina, were relieved by sublingual nitroglycerin. An exercise test revealed ST segment depression of 2 mV in lead V5 of the electrocardiogram. Coronary arteriography disclosed 99% stenosis with delay in segments 7 and 14, 90% stenosis in segment 10, and 25% stenosis in segment 1. Treatment with 100 mg of sustained-release diltiazem relieved some of the symptoms; when the dose was increased to 200 mg daily, no further chest pains were experienced. Patient 2 was a restaurant owner, aged 61 years, who reported attacks of chest pain during physical work. An exercise test revealed ST segment depression of 2 mV in lead aVF; coronary arteriography showed 99% stenosis in segment 7, 75% stenosis in segment 9, and 50% stenosis in segment 10. No attacks of chest pain were experienced after treatment with 200 mg of sustained-release diltiazem daily. Blood pressure, heart rate, and the rate-pressure product fell in both patients after diltiazem treatment.
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PMID:Sustained-release diltiazem in patients with effort angina and severe coronary artery sclerosis. 235 87

To clarify the role of coronary responses to nitroglycerin (NTG) in relieving myocardial ischemia, we examined the effects of NTG in canine models of dynamic and fixed coronary stenoses. Application of coronary stenosis in the proximal left circumflex artery decreased resting coronary blood flow by approximately 40% and caused a significant depression of left ventricular (LV) dP/dt. During fixed coronary stenosis created with an externally applied constrictor device, intravenous NTG, 5 micrograms/kg, reduced mean aortic pressure by 12 +/- 1.1 mm Hg (mean +/- SEM, p less than 0.01) and coronary blood flow by 9 +/- 1.0% (p less than 0.01) but did not affect stenosis resistance and LV dP/dt. During dynamic coronary stenosis produced with an intraluminal microballoon occluder, intravenous NTG caused a marked increase in coronary blood flow by 40 +/- 8.3% (p less than 0.01) and a decrease in stenosis resistance by 62 +/- 9.3% (p less than 0.01), as compared with postocclusion values, concomitant with a significant improvement in LV dP/dt. Intracoronary infusion of NTG, 1.0 microgram/kg/min, had few systemic and coronary hemodynamic effects during fixed coronary stenosis, whereas intracoronary NTG increased coronary blood flow and reduced stenosis resistance, depending on its dose, during dynamic coronary stenosis. These results indicate that NTG is capable of increasing coronary blood flow and alleviating myocardial ischemia due to direct stenosis-dilating effects related to the vasomobility of the coronary stenosis.
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PMID:Dilatation of coronary stenosis as the salutary effect of nitroglycerin in relief of myocardial ischemia in the dog. 241 Jun 91

A multicenter, double-blind placebo controlled study was designed to examine the efficacy of celiprolol in exercise induced angina pectoris. The study consisted of a 4-week placebo run-in period, 6-week titration, 4-week maintenance, 2-week tapering and a 2-week placebo run-out period. Entry criteria were a history of stable angina with chest pain and 1 mm ST segment depression between 3 and 12 min after start of treadmill exercise stress test. Patients started with celiprolol 200 mg daily for 2 weeks; non-responders received 400 mg daily for 2 weeks and then if necessary 600 mg daily for another 2 weeks. A 20% increase over baseline in exercise stress test to onset of angina was considered a response. Ninety-two patients were evaluated, 54 in the celiprolol group and 38 in the placebo group; 63 men and 29 women, mean age 57 years. The celiprolol group was significantly different from placebo after 6 weeks. In particular, exercise time increased by 4.3 min (placebo increased by 0.3 min), ST segment depression reduced by 0.4 mm, notwithstanding the increase in exercise time (placebo increased by 0.2 mm), maximum exercise heart rate reduced by 6 beats per min (placebo increased by 3 beats per min), maximum exercise systolic BP reduced by 14 mm Hg (placebo decreased by 1 mm Hg). The therapeutic success rate based on a 20% increase of exercise time was 85% after celiprolol and zero after placebo. Reduction in weekly angina attacks and nitroglycerin consumption was from 8 to 3 after celiprolol and from 9 to 6 after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Celiprolol in the treatment of exercise induced angina pectoris. 242 44

Efficacy and safety of the new beta-adrenoceptor antagonist, bisoprolol, in treatment of stable angina pectoris were studied in 36 patients using two types of single-blind design. After 2 weeks of therapy with bisoprolol in doses of 5 mg to 10 mg a day, exercise duration and time to 1 mm of ST-segment depression were significantly prolonged in 7 out of 10 patients who had a positive treadmill exercise test before bisoprolol. Bisoprolol significantly reduced heart rate (HR), systolic blood pressure (SBP), and rate-pressure product (RPP) at peak exercise, which would account for the beneficial effect of bisoprolol on exercise tolerance. Bisoprolol also produced improvement in symptoms for 26 patients with stable effort angina, as indicated by decreased frequency of anginal attacks and nitroglycerin consumption with a once-a-day regimen. Ten patients had no attacks after 5 mg of bisoprolol, and three more did not develop angina after increasing the dose to 10 mg a day. These results suggest that bisoprolol will be a promising, efficacious, and safe drug for the treatment of stable angina pectoris.
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PMID:Clinical evaluation of bisoprolol in patients with stable angina pectoris: a preliminary report. 243 88

1. The effects of intracarotid administration of Bay K 8644 on the ECG pattern along with their reversal by antianginal drugs were investigated in anaesthetized rats. 2. Intracarotid injections of Bay K 8644 (0.5-50.0 micrograms kg-1) produced a dose-related transient increase in systemic blood pressure. 3. The pressor response was accompanied by ST segment elevation (0.5-10.0 micrograms kg-1), ST segment depression concomitant with the occurrence of arrhythmias (20.0 micrograms kg-1), or A-V block (50.0 micrograms kg-1). 4. ST segment elevation reached its maximal value within 15 s and could be observed for 30-240 s. 5. The increase in blood pressure was immediate (within 5 s) and short lasting (30-120 s). After the initial increase it returned to control levels (0.5-20.0 micrograms kg-1) or dropped below (50.0 micrograms kg-1). 6. The ST segment elevation caused by 5.0 micrograms kg-1 Bay K 8644 (submaximal dose) was blocked by antianginal drugs (e.g. nitroglycerin, nifedipine and diltiazem) and by the peripheral benzodiazepine receptor antagonist PK 11195. However, the pressor response was not blocked by any of the drugs used. 7. ST segment elevation (or depression) induced by intracarotid administration of Bay K 8644 provides a useful tool for the evaluation of potential antianginal drugs.
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PMID:Bay K 8644-induced changes in the ECG pattern of the rat and their inhibition by antianginal drugs. 244 88


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