From the Guidelines
Metoprolol works by selectively blocking beta-1 adrenergic receptors primarily found in the heart, preventing catecholamines like epinephrine and norepinephrine from binding to these receptors, resulting in decreased heart rate, contractility, and blood pressure. This mechanism of action is supported by the 2011 ACCF/AHA guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction, which states that beta blockers competitively block the effects of catecholamines on cell membrane beta receptors, reducing myocardial contractility, sinus node rate, and AV node conduction velocity 1. The guidelines also highlight the importance of beta-1 adrenergic receptors in the myocardium, which are primarily targeted by metoprolol.
The benefits of metoprolol's mechanism of action are further supported by studies on its use in patients with heart failure, such as the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), which demonstrated a 34% reduction in mortality in patients treated with metoprolol succinate compared to placebo 1. Additionally, the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction recommend the use of beta blockers, including metoprolol, in patients with MI without contraindications, citing their ability to reduce myocardial oxygen demand and improve coronary perfusion 1.
Key points about metoprolol's mechanism of action include:
- Selective blockade of beta-1 adrenergic receptors in the heart
- Reduction in heart rate, contractility, and blood pressure
- Decreased myocardial oxygen demand
- Improved coronary perfusion
- Potential benefits in patients with heart failure, hypertension, and angina
Overall, metoprolol's mechanism of action makes it an effective treatment for various cardiovascular conditions, including hypertension, angina, heart failure, and myocardial infarction, with its selective blockade of beta-1 adrenergic receptors providing a therapeutic benefit while minimizing potential side effects.
From the FDA Drug Label
Metoprolol is a beta 1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta 2-adrenoreceptors, chiefly located in the bronchial and vascular musculature The mechanism of the antihypertensive effects of beta-blocking agents has not been fully elucidated However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity The mechanism of action of metoprolol is through beta 1-selective adrenergic receptor blockade, which leads to:
- Reduction in heart rate and cardiac output
- Decreased systolic blood pressure
- Inhibition of isoproterenol-induced tachycardia
- Reduction of reflex orthostatic tachycardia The possible mechanisms of antihypertensive effects of metoprolol include:
- Competitive antagonism of catecholamines
- Central effect leading to reduced sympathetic outflow
- Suppression of renin activity 2
From the Research
Mechanism of Action of Metoprolol
- Metoprolol is a beta-blocker that works by inhibiting chronic beta-1 stimulation-induced myocardial apoptosis/necrosis/inflammation 3
- It blocks beta 1 receptors without blocking beta 2 receptors, which is known as cardioselectivity 4
- This cardioselectivity is considered to be of potential importance in patients with obstructive airways disease, patients with peripheral vascular disease, and patients with insulin-dependent diabetes during hypoglycemic crisis 4
- Metoprolol does not have significant partial agonist activity or membrane-stabilizing activity 4
Effects on the Body
- Metoprolol reduces mortality and morbidity in combination with diuretics and angiotensin-converting enzyme inhibitors in patients with heart failure 5
- It improves left ventricular function, reduces hospitalizations for heart failure, and reduces mortality in patients with heart failure 5
- Metoprolol is effective in preventing heart failure in the post-MI period and as first-line agents in the treatment of young/middle-aged hypertension 3
- It is also effective in reversing left ventricular hypertrophy (LVH) in young/middle-aged hypertensives 3
Pharmacological Characteristics
- Metoprolol is a lipophilic beta-blocker that appears in high concentrations in human brain tissue and is associated with side-effects such as insomnia, dreams, and nightmares 3
- It has a longer elimination half-life and produces less interindividual variation in steady-state plasma concentrations compared to more water-soluble beta-blockers 4
- Metoprolol penetrates the central nervous system less readily compared to more lipophilic beta-blockers 4