Metoprolol action mechanism
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Mechanism of Action of Metoprolol
Introduction to Metoprolol
Metoprolol is a selective beta-1 adrenergic receptor antagonist widely used in the treatment of cardiovascular conditions such as hypertension, angina pectoris, and heart failure. Its therapeutic effects are primarily attributed to its ability to block beta-1 adrenergic receptors in the heart, leading to a reduction in heart rate and myocardial contractility 59.
Beta-1 Adrenergic Receptor Blockade
Metoprolol's primary mechanism of action involves the selective inhibition of beta-1 adrenergic receptors. This blockade reduces the effects of catecholamines (e.g., adrenaline and noradrenaline) on the heart, leading to decreased heart rate, myocardial contractility, and cardiac output. This action is beneficial in conditions like hypertension and angina, where reducing the workload on the heart is crucial 59.
Impact on Myocardial Function and Energetics
In patients with nonischemic dilated cardiomyopathy, metoprolol has been shown to improve left ventricular performance and myocardial efficiency. This improvement is achieved without increasing myocardial oxygen consumption, suggesting enhanced myocardial energetics. The drug also favorably alters substrate utilization, shifting from fatty acid to carbohydrate metabolism, which is more efficient for the failing heart .
Repression of PGC1alpha-Mediated CPT-1B Expression
Metoprolol decreases the expression of carnitine palmitoyltransferase-1B (CPT-1B) in diabetic hearts by repressing PGC1alpha-mediated coactivation of PPAR-alpha and MEF-2A. This repression is associated with increased binding of upstream stimulatory factor-2 (USF-2) to PGC1alpha, which suggests that USF-2 mediates the metoprolol-induced repression of PGC1alpha. This mechanism may partly explain the beneficial effects of metoprolol in heart failure .
Electrophysiological Effects
Metoprolol exhibits class II antiarrhythmic properties by selectively targeting cardiac beta-1 adrenergic receptors. It can affect cellular electrophysiological activity by decreasing the duration and voltage of the action potential plateau in ventricular myocytes. Additionally, metoprolol can inhibit sodium (INa), "L"-type calcium (ICa), and transient outward (Ito) or inward rectifying potassium (IKl) currents, which may contribute to its antiarrhythmic effects .
Neutrophil Modulation and Infarct Size Reduction
Recent studies have shown that metoprolol reduces infarct size in acute myocardial infarction (AMI) patients by targeting the haematopoietic compartment. It inhibits neutrophil migration in an ADRB1-dependent manner, impairing the structural and functional rearrangements needed for productive engagement of circulating platelets. This action reduces inflammation and reperfusion injury, highlighting a novel mechanism of metoprolol beyond its effects on cardiomyocytes .
Diuretic Effect
Metoprolol has also been observed to increase urine output significantly, likely due to an increase in renal blood flow and glomerular filtration rate. This diuretic effect can be beneficial in managing fluid overload in heart failure patients .
Conclusion
Metoprolol's mechanism of action is multifaceted, involving beta-1 adrenergic receptor blockade, modulation of myocardial energetics, repression of specific gene expressions, electrophysiological effects, and anti-inflammatory actions. These combined effects make metoprolol a versatile and effective agent in the management of various cardiovascular conditions.
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