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

1. The effects of propranolol, atenolol (ICI 66,082), practolol and pindolol on heart rate and maximal left ventricular dp/dt, atrioventricular conduction time, mean aortic flow and diastolic blood pressure during cardiac pacing were investigated over a wide dose range (0.025-4.0 mg/kg, i.v.) in dogs anaesthetized with pentobarbitone.2. Propranolol and atenolol produced similar reductions in haemodynamic parameters. Propranolol had no further effect in dogs pretreated with atenolol. 3. Practolol tended to cause smaller reductions in the haemodynamic parameters than either propranolol or atenolol. Subsequent administration of propranolol still had some depressant activity. 4. Pindolol produced a biphasic response, with depression of cardiac function at the low doses (0.025 and 0.1 mg/kg), but a reversal of effect as the dose was increased. 5. It is therefore concluded that, in anaesthetized dogs, the intrinsic activity of practolol and pindolol limits the fall in heart rate, cardiac conduction, aortic flow and maximal dp/dt observed with beta-adrenoceptor blockade. With pindolol, however, the influence of intrinsic activity is observed only in high doses related to beta-adrenoceptor blockade.
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PMID:The influence of the intrinsic sympathomimetic activity of beta-adrenoceptor antagonists on haemodynamic effects in anaesthetized dogs. 3 81

The subcutaneous administration of a single dose of the beta-adrenoceptor antagonists atenolol, betaxolol, oxprenolol, pindolol, propranolol, or sotalol to conscious spontaneously hypertensive rats (SHR) lowered mean arterial pressure (MAP) by 15-20%, but this vaso-depression was not accompanied by a rise in plasma norepinephrine (NE) concentration. When MAP was decreased at the same rate and to the same extent with the vasodilator minoxidil, plasma NE concentration increased 50-75%. Atenolol, betaxolol, propranolol, and sotalol lowered heart rate, whereas oxprenolol, pindolol, and minoxidil elicited a tachycardia. Atenolol (-48%), betaxolol (-63%), and propranolol (-29%) significantly suppressed plasma renin activity (PRA), and minoxidil elevated PRA by 150-315%. Pindolol (+37%) caused a nonsignificant increase in PRA, and oxprenolol (-23%) and sotalol (-17%) produced nonsignificant decreases in PRA. Because the beta-adrenoceptor antagonists did not increase plasma NE concentration, whereas an equivasodepressor dose of minoxidil did, we conclude that plasma NE concentration is inappropriately low relative to the decrease in MAP caused by beta-adrenoceptor antagonists in the conscious SHR. In addition, the diverse effects of the beta-adrenoceptor antagonists on PRA in SHRs indicate that a suppression of renin release cannot account for either the decrease in MAP caused by these drugs or the failure of plasma NE concentration to increase when MAP is decreased by beta-adrenoceptor antagonists.
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PMID:Response of plasma norepinephrine concentration to the vasodepression caused by beta-adrenoceptor antagonists in the conscious spontaneously hypertensive rat. 243 2

The effects of single oral doses of 10 mg felodipine and four beta-blockers (100 mg metoprolol, 5 mg pindolol, 80 mg propranolol, and 10 mg timolol) were evaluated alone and in combination in a 10-way crossover, double-blind, placebo-controlled trial in 10 healthy male volunteers randomized to the medication sequence according to a latin square design. Adverse effects were recorded from spontaneous complaints and investigator observations. Heart rate (HR), PR interval, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured supine, standing, and after treadmill exercise, before and 2 h after drug administration. The adverse effects experienced with felodipine were as expected for a vasodilator. Seven subjects mentioned complaints voluntarily on the combinations while three experienced side effects receiving felodipine or beta-blocker alone. Felodipine increased resting HR significantly. Timolol produced a greater depression of exercise heart rate than the other beta-blockers, indicating that the dose given was not equivalent to that of the other beta-blockers. Pindolol was ineffective in preventing the increase in supine HR produced by felodipine. Felodipine did not alter PR interval at any level of activity, but rate-corrected supine PR interval was prolonged slightly by felodipine. Metoprolol and timolol significantly prolonged standing PR interval. All beta-blockers prolonged exercise PR interval. Felodipine/beta-blocker combinations did not prolong PR interval more than beta-blockers alone. Prolonged PR interval was the result of reduced HR and direct inhibition of atrioventricular (AV) conduction. Only timolol and the timolol/felodipine combination lowered supine systolic blood pressure significantly. Timolol and all beta-blocker/felodipine combinations reduced exercise SBP significantly.
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PMID:Tolerance and cardiovascular effects of single dose felodipine/beta-blocker combinations in healthy subjects. 244 12

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

1. Ambulatory electrocardiography was used to compare the effects of propranolol and pindolol on symptoms, heart rate, arrhythmias and ST segments. Seventeen males (mean age 54 years) with a diagnosis of chronic stable angina pectoris (New York Heart Association Class II-III) were studied. Patients were treated on a double-blind cross-over basis with propranolol 80 mg three times daily or pindolol 5 mg three times daily for 14 days each. During the last 48 h of each treatment period ambulatory electrocardiography was performed. 2. Propranolol resulted in a significantly lower mean hourly, mean 24 h and minimum heart rate. Likewise propranolol caused a lower mean daytime and nocturnal heart rate. There was no significant difference in the frequency of angina between the treatments. The number of episodes of ST segment depression was not significantly different between the two drugs, although there was a trend in favour of propranolol. 3. Both the mean 24 h ST level and the maximum ST segment depression were lower during treatment with pindolol. Propranolol was associated with a total of 117 nocturnal pauses or episodes of asystole ranging in length from 1.5 to 2.8 s. During treatment with pindolol only one such period occurred. The number of premature ventricular contractions occurring during treatment with pindolol (1316 beats) was less than on propranolol (2010) and the mean hourly frequency of premature ventricular contractions was significantly lower during pindolol administration. 4. Pindolol is not significantly different from propranolol in the control of symptomatic and asymptomatic myocardial ischaemia and is associated with fewer premature ventricular contractions. However, there is no advantage in using pindolol in chronic stable angina.
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PMID:The influence of beta-adrenoceptor blockers with and without intrinsic sympathomimetic activity on heart rate, arrhythmias and ST-T segments, using ambulatory electrocardiography. 335 81

The effects of the beta-adrenergic blocking agent bucumolol [dl-5-methyl-8-(2-hydroxy-3-t-butylaminoproxy)coumarin] and its optical isomers were compared with those of propranolol and pindolol on the functional refractory period and the conduction time of atrioventricular (A-V) transmission in dogs. In dogs with intact nerves anesthetized with pentobarbital, bucumolol and propranolol (30 micrograms - 1 mg/kg) prolonged both parameters by blockade of background sympathetic nervous tone to A-V conduction. The optical d- and l-isomers of bucumolol depressed A-V conduction almost in parallel with their beta-blocking actions. In dogs with cardiac sympathectomy and bilateral vagotomy, or pretreated with reserpine, the dromotropic activity was lowered and the beta-blocking dose (30 micrograms - 1 mg/kg) of bucumolol and propranolol had less effect on A-V conduction, while larger doses (3-10 mg/kg) produced additional depression of the conduction. Pindolol, on the other hand, had a positive dromotropic action, reflecting its intrinsic stimulatory action. It is concluded that A-V conduction is affected by the existing tone of sympathetic nervous activity and that bucumolol has no beta-stimulant action and depresses A-V conduction by beta-blockade and by a non-specific action.
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PMID:Assessment of beta-blockade and the non-specific effect of bucumolol, a beta-adrenergic blocking agent, on atrioventricular conduction in anesthetized dogs. 612 36

beta-Adrenoceptor-blocking agents constitute a heterogeneous group of compounds. Membrane- stabilizing (quinidine-like) effects can be demonstrated pharmacologically with most compounds, but only at relatively high concentrations. There is no evidence to suggest that this property is of clinical relevance. Some compounds have a certain selectivity for receptors of the beta 1-type, whereas others possess beta-adrenoceptor stimulant activity (partial agonism). The clinical importance of these latter properties remains controversial. The selectivity for beta 1-adrenoceptors, which can be demonstrated pharmacologically for atenolol, metoprolol, and practolol, appears quite broad. Nevertheless a clear advantage over nonselective compounds with respect to their effects on lung function and vascular resistance in patients has not been established. There are two possible explanations. The first is that the doses used therapeutically may lie outside the selective range; the second is that most tissues appear to possess and mixed population of beta 1- and beta 2-adrenoceptors. According to our present understanding, even absolute specificity for a given subtype cannot provide organ or tissue specificity. Partial agonists provide a constant stimulation of beta-adrenoceptors while at the same time preventing access of catecholamines to the receptor they occupy. With some compounds (e.g., pindolol), stimulant activity may be sufficient to counterbalance the myocardial depression normally resulting from blockade of basal sympathetic tone. Heart rate and cardiac output are thus maintained within normal limits and compensatory increases in vasomotor tone (seen with antagonists lacking intrinsic activity) do not occur. Pindolol has been shown to dilate blood vessels at very low doses and to produce significant relaxation of isolated tracheal smooth muscle at concentrations within the range of therapeutic plasma levels found in humans. These effects may underly the relatively low incidence of bronchopulmonary and vascular side effects reported for this compound.
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PMID:Beta-adrenoceptor-blocking agents: are pharmacologic differences relevant? 612 93

The use of beta adrenoceptor blockade in the treatment of rest angina is controversial, and the effects on severe angina of partial agonist activity in beta blockers are unknown. Eight patients with effort angina and seven with effort and nocturnal angina and severe coronary artery disease were studied initially when they were not taking any antianginal drugs. Pindolol 5 mg thrice daily (with partial agonist activity) and atenolol 100 mg daily (without partial agonist activity) were given for five days each in a double blind randomised manner. Diaries of angina were kept and treadmill exercise testing and ambulatory ST monitoring performed during the last 48 hours of each period of treatment. Daytime and nocturnal resting heart rates and the frequency of angina were significantly reduced by atenolol compared with pindolol (p less than 0.01). The duration of exercise was significantly increased and the frequency, duration, and magnitude of daytime and nocturnal episodes of ST segment depression on ambulatory monitoring were reduced by atenolol. Reduction in resting heart rate is important in the treatment of both effort and nocturnal angina. Partial agonist activity in beta adrenoceptor antagonists may be deleterious in patients with severe angina pectoris.
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PMID:Effect of partial agonist activity in beta blockers in severe angina pectoris: a double blind comparison of pindolol and atenolol. 614 91

The effects of intravenous (0.4 mg) and oral pindolol (5 mg, t.i.d.) on exercise tolerance and electrocardiographic ST-segment changes were investigated in 20 patients with documented coronary artery disease (16 males and 4 females; mean age, 56.7 years). A randomized double-blind crossover design was used, and graded submaximal exercise was performed on a bicycle ergometer. Pindolol significantly decreased heart rate at rest, and during and after exercise. The time intervals before the appearance of ST depression, before anginal pain, and before the cessation of work were significantly increased after beta-adrenergic blockade, and work tolerance was enhanced, both indicating that pindolol is an effective antianginal agent. Angina appeared at a lower heart rate after pindolol. Anginal pain and cessation of work were associated with significantly less ST-segment depression after pindolol, suggesting that the relation between ST depression and myocardial ischemia is altered by beta-adrenergic blockade. The appearance and disappearance of ST-segment changes correlated closely with heart rate during placebo and pindolol treatment. Heart rate thus seems to be a major determinant of ST-segment depression during and after exercise in coronary artery disease.
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PMID:Effect of intravenous and oral pindolol on exercise tolerance and electrocardiographic changes in angina pectoris. 616 Mar 24

The effect of placebo, isosorbide dinitrate (ISDN) (5 mg orally), pindolol (1.0 mg i.v.) and the combination of ISDN and pindolol was tested in 12 patients with stable, exercise-induced angina pectoris and normal resting ECG. A graded submaximal exercise test was performed on a bicycle ergometer 30 min after medication. All patients had ST depression during and shortly after exercise. ISDN and pindolol increased exercise tolerance to a similar degree but through different mechanisms. Pindolol decreased heart rate and markedly reduced ST depression in the ECG, while ISDN had no effect on ECG changes. The combination of ISDN and pindolol was superior to either drug alone in increasing exercise tolerance in angina pectoris.
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PMID:The effect of pindolol and isosorbide dinitrate and their combination on exercise tolerance and ECG changes in angina pectoris. 701 79


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