Disease relevance of metoprolol

• We compared the effects of weight reduction, metoprolol, and placebo on M-mode echocardiographic measurements of the thickness and mass of the left ventricular wall in a 21-week, randomized controlled trial that enrolled 41 young, overweight patients with hypertension [1].
• During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias [2].
• A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias [2].
• The 55 patients whose arrhythmia was noninducible during the initial electrophysiologic test were also treated with metoprolol [3].
• Treatment of migraine with metoprolol [4].

Psychiatry related information on metoprolol

• Metoprolol for intermittent explosive disorder [5].
• These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients [6].
• Successful prophylaxis of recurrent transient global amnesia with metoprolol [7].
• Efficacy of low-dose metoprolol in neuroleptic-induced akathisia [8].
• Oral dosing of metoprolol produced no significant changes in reaction time [9].

High impact information on metoprolol

• As compared with metoprolol therapy, electrophysiologically guided antiarrhythmic drug therapy did not improve the overall outcome of patients with sustained ventricular tachyarrhythmias [3].
• The incidence of symptomatic arrhythmia and sudden death combined was virtually the same in the two groups with inducible arrhythmia after two years of observation (electrophysiologically guided therapy vs. metoprolol therapy, 46 percent vs. 48 percent) [3].
• At the end of the follow-up period, the patients in the weight-reduction group had lost an average of 8.3 kg, and their blood pressure had decreased by an average of 14/13 mm Hg, as compared with 12/8 mm Hg in the metoprolol group and 9/4 mm Hg in the placebo group [1].
• The changes in thickness of the interventricular septum and the left ventricular mass in the weight-reduction group were also greater than those in the metoprolol group [1].
• However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05) [2].

Chemical compound and disease context of metoprolol

• Propranolol caused severe bradycardia and raised diastolic blood-pressure during hypoglycaemia; these effects were milder with metoprolol [10].
• Ventricular arrhythmias were prevented or significantly slowed by sotalol in 11 of 19 studies (58%) compared with in one of 14 (7%) studies with metoprolol [11].
• Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease [12].
• In the last year, two large randomized controlled trials of metoprolol (MIAMI, almost 6,000 patients) and atenolol (ISIS 1, over 16,000 patients) given intravenously within 12 hours of the onset of acute myocardial infarction reduced mortality by about 15% in low-risk subjects [13].
• At equivalent beta-adrenoceptor blocking doses, however, carvedilol, but not metoprolol, attenuated the increase in collagen content in noninfarcted regions and prevented the increase in right ventricular weight/body weight (all p < 0.05), and its effect was similar to captopril [14].

Biological context of metoprolol

• Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06) [15].
• During withdrawal of metoprolol, the heart rate and left atrial dimension increased (p less than 0.0001), whereas ejection fraction decreased (p less than 0.0001) [16].
• For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure [17].
• Coronary vascular resistance did not rise in either group after selective beta 1-blockade with metoprolol [18].
• Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial [19].

Anatomical context of metoprolol

• Specific binding in the presence of 10(-5) M metoprolol was reduced approximately 75% for both arterioles and myocytes [20].
• Immediately after thrombotic occlusion of the left anterior descending coronary artery, the cardioselective beta-blocking agent metoprolol was given intravenously at a dose of 0.5 mg/kg infused over 10 min [21].
• Additionally, patients treated with metoprolol had an increased percentage of T cells, natural killer cells, and increased interleukin-2 receptor density upon stimulation with concanavalin A [22].
• CONCLUSIONS: It appears that patients with dilated cardiomyopathy who are treated with metoprolol have enhancement of cell-mediated immunity and improvement of T-cell function; these improvements are correlated to improvement in ejection fraction [22].
• At branching sites in the thoracic aorta, immunoglobulin G incorporation and endothelial cell replication were significantly greater in untreated monkeys than in metoprolol-treated monkeys (p less than 0.01 for both analyses); no differences existed at nonbranch sites [23].

Associations of metoprolol with other chemical compounds

• The frequency rates of responders (diastolic blood pressure, less than or equal to 95 mm Hg) in the metoprolol group and the hydrochlorothiazide group were 50% and 47% after four weeks and 65% and 61% after eight weeks, respectively [24].
• On the other hand, alpha-blocker phentolamine and beta 1-blocker metoprolol did not abolish the stimulation of AdC in PST by ISO [25].
• MEASUREMENTS AND MAIN RESULTS: Resting systolic blood pressure measured without drug therapy was lowered markedly after exercise conditioning on placebo (146 to 135 mm Hg) and on metoprolol (144 to 133 mm Hg) (P less than 0.05), but not on propranolol (no change) [26].
• Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade [17].
• METHODS AND RESULTS: Fifteen patients with New York Heart Association class III-IV CHF secondary to dilated cardiomyopathy were titrated to a minimum dose of metoprolol 25 mg BID on a background therapy of digoxin, diuretic, and angiotensin-converting enzyme inhibitors [22].

Gene context of metoprolol

• Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity [27].
• This index correlated with the 4'-hydroxylation of S-mephenytoin (rs = -0.51, p < 0.01), but not with the alpha-hydroxylation of metoprolol, implying that imipramine N-demethylation is under a coregulatory pharmacogenetic control of CYP2C19, but not of CYP2D6 [28].
• In contrast, metoprolol, a compound with similar permeability but no affinity for PGP had no effect on PGP expression [29].
• 4. RU 24969 (7.5 mg kg-1 i.p.)-induced hyperlocomotion was inhibited by the (-)-, but not (+)-isomers of pindolol (4 mg kg-1) and propranolol (20 mg kg-1) but not by metoprolol (10 mg kg-1) or ICI 118,551 (5 mg kg-1), consistent with an involvement of 5-HT1A or 5-HT1B receptors [30].
• Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone [31].

Analytical, diagnostic and therapeutic context of metoprolol

• Drug therapy: metoprolol [32].
• Antihypertensive treatment with metoprolol or hydrochlorothiazide in patients aged 60 to 75 years. Report from a double-blind international multicenter study [24].
• CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being [33].
• Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily [34].
• 30 patients (10 normotensive, 20 hypertensive) with stable angina and positive treadmill exercise tests entered a double-blind, placebo-controlled crossover trial of metoprolol, 100 mg twice daily [35].

References