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)

Changes in the exercise ECG caused by five different drugs are presented. Analysis of these changes indicate that these are related to the hemodynamic effects of the drugs, rather than to reduction of myocardial ischemia. Calcium antagonists (Verapamil) as well as drugs which reduce heart rate (Alinidine, Propranolol) do not change the relation between ST depression and heart rate in a given patient. Drugs which lower ventricular volume (Molsidomine, Nitroglycerine) reduce the amount of ST depression at the same heart rate during exercise.
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PMID:The effects of drugs on the exercise electrocardiogram. 731 92

The effects of the ionophore RO2-2985 (X537A) on KCl- and histamine-induced contractions in porcine coronary vascular smooth muscle were studied in vitro. Cumulative dose-response curves were constructed for KCl and histamine in the presence and absence of RO2-2985. The dose-response curve to KCl in the presence of RO2-2985 was shifted to the right with no change in the maximal response attained. Lineweaver-Burk and Hill plots indicated that responses to KCl involved a positive cooperative interaction between excitation and some step or steps in the contractile event and that RO2-2985 increased this cooperativity. The dose-response curve to histamine in the presence of the ionophore was significantly shifted to the right with a 40 to 50% depression in the maximal response. Propranolol inhibited norepinephrine-induced relaxation of KCl-contracted coronary strips but did not affect RO2-2985-induced relaxation. These results suggest that RO2-2985 competitively inhibits KCl-induced contractions but inhibition of histamine-induced contractions are of a mixed mechanism. Also, RO2-2985 does not appear to induce relaxation of coronary artery smooth muscle by liberating enodgenous catecholamines. Preliminary evidence supports involvement of prostaglandins in the mechanism of ionophore-induced coronary relaxation.
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PMID:Differential inhibitory effects of the ionophore RO2-2985 (X537A) on contractile responses to potassium and histamine in coronary artery smooth muscle. 735 71

A catheter-tip velocity transducer with two high-fidelity pressure manometers was used to evaluate the left ventricular (LV) hemodynamic effects of intravenous propranolol (10 mg). Nine patients without clinical evidence of heart failure were studied. Pulsatile ascending aortic blood flow velocity and pressure and LV pressure were measured continuously during drug administration. Beat-to-beat changes in stroke volume index, stroke work index, LV end-diastolic pressure, maximum blood flow velocity and acceleration, and maximum LV dP/dt were determined. Propranolol produced a decrease in maximum blood flow velocity (from 58 +/- 4.7 to 42 +/- 5.1 cm/sec, p less than 0.002), and acceleration (from 1181 +/- 130 to 847 +/- 117 cm/sec2, p less than 0.002, max dP/dt (from 1361 +/- 70 to 1146 +/- 63 mm Hg/sec, p less than 0.002), stroke volume index (from 47 +/- 3.0 to 38 +/- 3.2 ml/m2, p less than 0.002) and total stroke work index (from 702 +/- 33 to 603 +/- 44 mJ/m2 p less than 0.04), with little change in mean aortic pressure, peak systolic pressure and LV end-diastolic pressure. Depression in myocardial function was detectable within 1 minute after initiation of propranolol and persisted when negative chronotropic effects were eliminated by atrial pacing. The multisensor catheter technique allows rapid and safe detection of changes in cardiovascular function during propranolol administration in conscious man.
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PMID:Use of catheter-tip velocity--pressure transducer to evaluate left ventricular function in man: effects of intravenous propranolol. 736 37

Vasodilator responses to dopexamine, fenoldopam and dopamine, which are known to have agonist activity at D1-dopamine receptors, were examined in the rat isolated perfused kidney preparation. Perfusion pressure was raised by perfusing with the thromboxane TxA2 analogue, U46619, and vasodilator responses were observed as dose-related falls in perfusion pressure. Propranolol (10(-6) M) and prazosin (10(-6) M) were present throughout to eliminate beta 2 and alpha 1-adrenoceptor-mediated responses, respectively. The vasodilator responses were antagonized by SCH23390 (10(-9) M), indicating that they were mediated via D1-receptors. The displacements of the dose-response curves for fenoldopam, dopexamine and dopamine were, however, non-parallel with significant depression of the maxima to 30.2, 37.9 and 34.3%, respectively. In the presence of SCH23390 (10(-8) M) and prazosin (10(-6) M), dopexamine, isoprenaline and noradrenaline produced dose-related renal vasodilation. This was antagonized by propranolol indicating a role for beta-adrenoceptors. In the case of dopexamine, the maximum response was depressed in the presence of propranolol. The reason for the atypical blockade of vasodilator responses by SCH23390 was investigated. One possibility was the appearance of transient vasoconstrictor responses at higher doses of fenoldopam, dopexamine and dopamine, usually preceding the vasodilatation. The possibility was therefore considered that the vasoconstriction may have opposed the usual vasodilation at high doses and thus limited the size of the maximum vasodilation in the presence of SCH23390. The vasoconstriction by fenoldopam was not antagonized by S-sulpiride, the D2-receptor antagonist but was blocked by mianserin and therefore attributed to 5-HT2 receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atypical antagonism of D1-receptor-mediated vasodilator response in the perfused kidney by SCH23390. 747 26

The cardiovascular actions of combined intravenous (i.v.) diltiazem and propranolol were studied in barbiturate-anesthetized dogs. When given alone, diltiazem increased cardiac output (CO) and P-R interval duration (P-R) while decreasing mean arterial pressure (MAP), heart rate (HR), and systemic vascular resistance (SVR). Propranolol alone decreased CO and HR while increasing SVR. With the same i.v. doses, combined infusion of diltiazem and propranolol rapidly resulted in depression of CO to levels similar to those achieved with propranolol beta-adrenoceptor blockade alone. The combination decreased MAP to levels achieved with diltiazem-induced calcium channel blockade. P-R increased beyond the durations produced by either drug given alone. Pharmacokinetic interactions were not apparent, although slight increases in propranolol plasma concentrations were observed during combined drug infusions. These studies support clinical observations that the cardiovascular effects resulting from a combination of diltiazem and propranolol may be attributed to the characteristic cardiovascular actions of each individual drug.
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PMID:Cardiodepressant actions of combined diltiazem and propranolol in dogs. 751 32

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
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PMID:Antianginal effects of YM-16151-4 in various experimental angina models. 768 38

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases. The exercise-induced tachycardia was maintained within 12% of pre-dose levels, presumably by withdrawal of vagal tone.5. Cardiac inotropism, as indicated by dPLv/dt max, was not affected by ZD7288 or zatebradine at rest,although the inotropic response to exercise decreased in proportion to the decreases in exercise-induced tachycardia. Propranolol caused a marked dose-dependent decrease in the exercise-induced inotropic response (by 85% at 0.3mg kg-1).6. Whilst the sino-atrial node modulators increased stroke volume at rest, and augmented increases in response to exercise, propranolol did not affect resting stroke volume and decreased the responses to exercise.7. Cardiac output at rest and cardiac output increases during exercise were well maintained in the presence of ZD7288 and zatebradine in contrast to propranolol which induced a significant depression of cardiac output, both at rest and during exercise. Propranolol also caused significant systemic vasoconstriction.8. In conclusion, ZD7288 has haemodynamic actions comparable to those of zatebradine despite their chemical dissimilarity. ZD7288 may be of benefit in the treatment of ischaemic heart disease by reducing heart rate without impairing cardiac function.
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PMID:The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol. 785 51

Propranolol, 60 mg or less, was administered daily between 5:30 and 6:00 a.m. to 33 patients with winter depression. After open treatment with a mean dose of 33 mg/day, 24 patients (73%) met the remission criteria; 23 completed double-blind continuation or placebo substitution. Subjects who continued to receive propranolol had a mean increase in Hamilton depression score of 3.5, whereas patients switched to placebo had an increase of 11.2; the difference was statistically significant. These findings are consistent with the hypothesis that duration of nocturnal melatonin secretion is the critical seasonal time cue in humans.
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PMID:Early-morning administration of short-acting beta blockers for treatment of winter depression. 806 99

A new intranasal spray formulation of propranolol was developed to provide beta-adrenergic blocking medication on an immediate basis to patients with angina pectoris. The effects of this spray or placebo were assessed in 16 patients with effort-induced angina in a blinded, randomized, cross-over design study that compared placebo with intranasal propranolol spray (5 mg/puff) 15 minutes before exercise on a treadmill (Bruce protocol). One week later, each patient, acting as his/her own control, received the alternative treatment and repeated exercise. Mean plasma propranolol level with active therapy was 20 ng/ml. Patients with active spray demonstrated a significant increase in total exercise time than patients taking placebo (530 +/- 197 vs 460 +/- 177 seconds, p = 0.05), an increase in the time to 1 mm ST-segment depression on the electrocardiogram (384 +/- 202 vs 327 +/- 144 seconds, p < 0.05), and an increase in time to onset of angina (452 +/- 149 vs 363 +/- 175 seconds, p = 0.0005). There was a blunting of maximal exercise heart rate with active therapy compared with placebo (120 +/- 13 vs 133 +/- 17 beats/min, p < 0.01), blunting of maximal exercise systolic blood pressure (185 +/- 22 vs 194 +/- 21 mm Hg, p < 0.05), and blunting of peak double product (p < 0.0005), with more modest effects on resting heart rate. Propranolol spray is an effective approach for providing immediate beta blockade and improving exercise tolerance in patients with angina pectoris.
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PMID:Improvement in exercise tolerance and immediate beta-adrenergic blockade with intranasal propranolol in patients with angina pectoris. 821

Calcium-antagonist and B-blockers are effective in improving exercise tolerance in patients with effort angina. We studied the short effects of oral administration of nifedipine (10 mg) and propranolol (80 mg) alone and in combination in 15 elderly patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 15 patients (13 men and 2 women, mean age 69 years) performed symptoms-limits bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration, real time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by drug alone and in combination. Propranolol and nifedipine improved exercise duration in combination; however, a different response to the three pharmacologic interventions was found in patients treated with single drug. The improvement in exercises tolerance was associated with rate-pressure product values at peak exercise tolerance was associated with rate-pressure product values at peak exercise, unchanged after placebo and significantly reduced after both propranolol alone and in combination. After placebo all patients had exercise-induced angina, in 50% and in 40% after propranolol and the combination of the two drugs, respectively. In aging patients nifedipine and propranolol are effective in the treatment of effort angina and they are superior in patients who show poor response to mono therapy, although this combination will be conditioned by different patient sensibility to the three pharmacologic interventions and then therapeutic choice would be evaluated and verified individually.
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PMID:[Acute effects of propranolol and its association with nifedipine in aged patients with effort stable angina. Randomized double-blind crossover study, under placebo control]. 833 70


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