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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacological activity of N-[2-(2,6-dimethoxyphenoxy) ethyl]-2-(2-methoxyphenoxy) ethanaminium chloride (ACC-7513) was determined in isolated smooth and cardiac muscle and its effect on blood pressure and heart rate assessed in the spontaneously hypertensive rat (SHR). ACC-7513 was found to be a potent alpha-adrenoceptor blocking agent (pA2:8.33) and a 5-hydroxytryptamine (5-HT) antagonist (pA2:7.01), both in rabbit aortic strips. The affinity for alpha-adrenoceptors was about 20 times greater than that for 5-HT-receptors. High concentrations of ACC-7513 did not block histamine in rabbit aortic strips, or beta 1- or beta 2-adrenoceptor responses induced by isoprenaline in guinea-pig right atria and trachea, respectively, but did block cholinoceptor responses induced by carbachol in rat uterus, non-competitively. High concentrations of ACC-7513 also produced sino-atrial depression in guinea-pig right atria and direct relaxation of depolarized rabbit aortic strips. ACC-7513 depressed blood pressure of conscious SHRs and produced a reflex increase in heart rate. The reductions in pressure were modest and of short duration. It is concluded that: (a) ACC-7513 is a potent, selective alpha-adrenoceptor and 5-HT receptor antagonist; and (b) ACC-7513 is not likely to be useful in the treatment of hypertension.
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PMID:Pharmacological activity of ACC-7513, a selective alpha-adrenoceptor and 5-hydroxytryptamine receptor blocking agent. 286 Sep 40

The effects of acute intravenous administration of ICI 118,587 (Corwin), a partial beta 1 agonist, were studied in nine patients with dilated cardiomyopathy and symptomatic congestive heart failure. Hemodynamic and metabolic parameters were measured using Swan-Ganz, arterial, and coronary sinus catheters. Repeated doses of Corwin produced no significant change in left ventricular performance, while a trend towards decreased blood pressure and stroke work was seen. No change occurred in coronary sinus blood flow, transmyocardial lactate extraction, or catecholamine release. One patient had significant depression of left ventricular function with hypotension. Thus, acute infusion of Corwin produced no beneficial inotropic responses, but rather produced features suggestive of further myocardial depression.
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PMID:Acute hemodynamic and metabolic effects of ICI 118,587 (Corwin), a selective partial beta 1 agonist, in patients with dilated cardiomyopathy. 286 73

Colterol, procaterol, sulfonterol, terbutaline and three monophenolic derivatives of terbutaline were examined with respect to their ability to react in vitro on beta-adrenoceptors in tissues isolated from guinea-pig. The effects measured were a) relaxation of the tracheal smooth muscle (mostly beta 2), b) depression of subtetanic contractions of the soleus muscle (beta 2), and c) increase in the force of the papillary muscle of the left ventricle (beta 1). Antagonistic effects were measured against isoprenaline as an agonist. The compounds studied showed a wide variation in selectivity, potency and intrinsic activity. All agonists showed a pronounced beta 2-selectivity, in general characterized by a higher intrinsic activity at beta 2- than at beta 1-adrenoceptors, while differences in affinity, as judged from the pA2-values were small. Partial agonists, such as sulfonterol, which did not cause a complete relaxation of a moderately contracted tracheal muscle, produced identical concentration-response curves from the trachea and soleus muscle. It is concluded that partial agonism at beta 1-adrenoceptors is an important factor for functional selectivity of beta 2-adrenoceptor agonists. On the other hand there seems to be no useful differences between the maximum effect elicited by a partial beta 2-adrenoceptor agonist on the skeletal muscle as compared with airway smooth muscle.
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PMID:Partial agonism and functional selectivity: a study on beta-adrenoceptor mediated effects in tracheal, cardiac and skeletal muscle. 287 66

To assess the effects of bevantolol on stable angina pectoris of effort and its impact on metabolic risk factors, a comparison study of this beta 1-blocking agent and atenolol was undertaken in 40 subjects (mean age 51 years). After a 4-week, single-blind, placebo washout period, 12 men and 8 women were randomized to receive 150 mg of bevantolol twice daily and 12 men and 8 women to treatment with 100 mg of atenolol once daily in a parallel, double-blind, 12-week treatment phase. Patients were assessed at weeks 2, 6 and 12 after bicycle exercise until angina or ST-segment depression greater than or equal to 0.15 mV appeared. Concentrations of cholesterol lipoproteins and 3 prostaglandin metabolites were determined. One patient receiving bevantolol was withdrawn from the study because of insufficient efficacy and 2 receiving atenolol were withdrawn because of side effects. After 2 weeks of therapy, significant decreases were seen in both groups in the number of angina attacks, mean sitting heart rate, systolic and diastolic blood pressure, mean maximum heart rate during exercise and mean double-product of systolic blood pressure and heart rate at the end of exercise. There was a trend toward significance in the increase of mean duration of exercise and total work performed with both agents, although these values were not statistically significant. Both high density lipoproteins and the ratio of high density lipoproteins to low density lipoproteins increased in the bevantolol group and decreased in the atenolol group. These changes were statistically significant at week 6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of bevantolol and atenolol on symptoms, exercise tolerance and metabolic risk factors in angina pectoris. 287

Over 20 years ago, it was established that beta blockers could reduce high blood pressure. Currently, several beta blockers with different ancillary properties are available. They all have the property of blocking beta 1 receptors but differ from each other in a number of other respects: they may or may not block beta 2 receptors in low doses (beta 1 = receptor selectivity); they may or may not possess varying degrees of partial agonist activity, also known as intrinsic sympathomimetic activity (ISA); they vary in the extent to which they are soluble in fat (lipophilicity). A review of relevant published findings indicates that the effects of beta blockers on cardiac output are not essential for their antihypertensive effect, nor is penetration of these drugs into the brain and cerebrospinal fluid. Reduction in blood pressure during long-term beta blocker therapy is always associated with reduction of total peripheral resistance. Beta blockers with sufficient ISA to prevent cardio-depression, by exerting less negative inotropic and chronotropic effects on the heart, do not cause initial reflex vasoconstriction in response to cardiac beta blockade. Unlike beta blockers devoid of ISA, these agents ultimately reduce blood pressure by lowering the increased vascular resistance in hypertension to below pretreatment values. Recent beta blocker research has revealed a number of ways to manipulate the characteristically elevated vascular resistance in hypertension. Examples of these efforts are the combination of ISA, alpha 1 or alpha 2 receptor blockade and direct vasodilating properties in the enantiomers of a single beta blocker molecule. The practical significance of these developments remains to be established.
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PMID:Effect of beta blockers on vascular resistance in systemic hypertension. 288 73

Adverse effects of beta-adrenergic receptor blocking drugs can be divided into two categories: 1) those that result from known pharmacological consequences of beta-adrenergic receptor blockade; and 2) other reactions that do not appear to result from beta-adrenergic receptor blockade. Adverse effects of the first type include bronchospasm, heart failure, prolonged hypoglycemia, bradycardia, heart block, intermittent claudication, and Raynaud's phenomenon. Neurological reactions include depression, fatigue, and nightmares. It is not yet proven whether the beta 1-selective adrenergic blockers or those with partial agonist activity reduce the overall frequency of adverse reactions seen with propranolol. Patient age does not appear, in itself, to be associated with more beta-blocker side effects. Side effects of the second category are rare. They include an unusual oculomucocutaneous reaction and the possibility of oncogenesis. There are also many drugs that interact with beta-blockers, which may increase toxicity. Finally, there are specific patient characteristics where one beta-blocker may be more effective and safer than another.
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PMID:Beta-adrenergic receptor blockers. Adverse effects and drug interactions. 289 72

Animal investigations suggest that the mechanism of the antihypertensive effect of urapidil may be complex. Suggestions have included an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Peripheral alpha 1-blocking activity has been demonstrated in man, and a shift to the right in the dose-response curve to phenylephrine has been found after administration of urapidil, while responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal, but urapidil does not inhibit the exercise-induced increase in the heart rate, and there is only some suggestion of a possible inhibition of isoprenaline-induced tachycardia. Possible central activity may be deduced from the observation that while lower single doses reduce blood pressure and increase the heart rate, with higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, lower doses of urapidil lead to an increase in noradrenaline levels, while changes in renin are less constant, but there has been a report that a high dose reduced vanillylmandelic acid excretion. Urapidil reduces peripheral resistance along with arterial pressure, and cardiac output is increased. In spite of a reduced arterial pressure, renal blood flow is maintained, presumably due to dilation of renal vessels. Urapidil is well absorbed orally with a bioavailability of about 70% and a tmax at about 4 h after a sustained release capsule. It is metabolized in the liver with a t1/2 of 4.7 h. In conclusion there is evidence that urapidil is an alpha 1-blocking drug in man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology of urapidil. 290 95

Beta-adrenergic blockade with intrinsic sympathomimetic activity (ISA) causes less depression of resting and submaximal heart rate (HR) than non-ISA beta-blockers. The effects of these drugs on exercise haemodynamics have not been well studied. We evaluated effects of pindolol, propranolol and placebo during rest and steady-state exercise on cardiac output, oxygen consumption, calf blood flow, HR and blood pressure in 18 healthy subjects. Pindolol 5 mg and propranolol 80 mg given twice daily, reduced maximal exercise HR by 50 and 52 beats.min-1 respectively, confirming similarity of beta 1-blockade. Resting cardiac output was unchanged in all three groups after one week of therapy. Cardiac output, measured during steady-state exercise decreased in the propranolol group (18.3 vs 15.6 l.min-1) with no significant changes in pindolol (15.7 vs 16.01.min-1) or placebo (18.6 vs 17.3 l.min-1). The rise in cardiac output, from rest to exercise, was similarly attenuated by propranolol but not by pindolol or placebo. Exercise stroke volume increased 12% on pindolol (123-140 cc) and decreased 7% on propranolol (143-133 cc). Neither drug had a detrimental effect on exercise calf blood flow compared to placebo. Thus, unlike propranolol, pindolol with ISA, maintains a normal cardiac output during submaximal exercise.
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PMID:Exercise haemodynamic effects of beta-blockade and intrinsic sympathomimetic activity. 291 88

The acute effects of 10 mg of oral nisoldipine on hemodynamics, oxygen transport and metabolism, and distribution of cardiac output, at rest and during semiupright bicycle exercise, were evaluated in 10 men with effort angina receiving long-term beta 1 blockade. Cardiac output and leg blood flow were measured using the thermodilution technique. At rest, nisoldipine decreased systemic resistance from 18.9 +/- 1.0 to 15.9 +/- 1.2 dynes.s.cm-5.10(2) (p less than 0.05) and cardiac output increased from 4.8 +/- 0.2 to 5.3 +/- 0.3 liters/min (p less than 0.05) without changing leg blood flow. During maximal exercise with nisoldipine, systemic resistance was reduced (10.6 +/- 0.9 to 8.6 +/- 0.5 dynes.s.cm-5.10(2), p less than 0.05) and cardiac output increased 18% (10.3 +/- 0.7 to 12.2 +/- 0.6 liters/min, p less than 0.05) when compared with control values. Exercise heart rate was higher with nisoldipine (113 +/- 4 vs 106 +/- 4 beats/min, p less than 0.01), but the mean arterial pressure was not significantly changed, giving a higher rate-pressure product. The increase in mean pulmonary artery wedge pressure was attenuated (26 +/- 3 vs 30 +/- 3 mm Hg during control exercise, p less than 0.05), but ST depression was unaltered. Exercise leg flow was reduced by nisoldipine from 4.3 +/- 0.4 to 3.9 +/- 0.3 liters/min (p = 0.07) and the proportion of cardiac output distributed to the legs was reduced from 42 +/- 3 to 33 +/- 3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nisoldipine on systemic and leg blood flow, oxygen transport and metabolism, and hemodynamics during exercise in effort angina pectoris. 292 36

Numerous studies have been, and are being devoted to the nature of adrenergic and purinergic receptors in the bronchopulmonary system. Studies of beta-adrenoceptors performed with ligands (table I) have demonstrated the presence of two types of receptors, beta 1 and beta 2 in proportions of about 15 : 100 respectively; this proportion is approximately the same at all levels of the tracheobronchial tree. Beta-adrenoceptors (beta 1 + beta 2) are globally more numerous in peripheral organs which contain heterogeneous tissues. Their number can be modified in certain circumstances, notably in asthma, infection and after prolonged treatment with sympathomimetic amines. Functional studies using specific beta 1-adrenoceptor agonists (RO-363 or prenalterol) or determining the relative activities of beta 1 and/or beta 2 stimulants and their inhibition by selective beta-blockers have shown that stimulation of beta 1-adrenoceptors may produce partial relaxation of the isolated trachea but not of lung parenchyma, the latter being supposed to represent distal airways. Studies on isolated small bronchi, about 0.1 mm in diameter (fig. 1 and 2A) have confirmed that stimulation of beta 1-adrenoceptors has not effect on distal airways. They have also demonstrated that beta 2-stimulants have different intrinsic activities (fig. 2B). Studies of alpha-adrenergic receptors using ligands (table II) have shown that these receptors are in small number in the tracheobronchial tree of numerous animal species. Functional studies on the conscious guinea-pig have shown that clonidine can potentiate the bronchoconstrictor effects of acetylcholine, histamine and serotonin (fig. 3) and that this potentiating effect is specifically inhibited by yohimbine and piperoxan (fig. 4). This action of clonidine has been attributed to depression of the reflex sympathetic activity associated with bronchospasm. Alpha 1-adrenoceptor agonists (phenylephrine, methoxamine) induce contracture of the isolated bronchial smooth muscle (fig. 5) but may partially reduce the bronchoconstrictor effects of acetylcholine, histamine or serotonin (fig. 6). This last effect is partially inhibited by alpha 1-blockers (fig. 7) and seems to be due to shrinkage of the bronchial mucosa. Finally, studies of purinergic receptors in the bronchopulmonary system have shown that they probably are of the A2-P1 type (tables III and IV) and that they do not seem to be involved in the bronchodilator activity of theophylline.
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PMID:[Adrenergic and purinergic receptors and bronchial motoricity]. 299 53


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