What is the mechanism of action of metoprolol (beta-1 selective adrenergic receptor blocker)?

From the Guidelines

Metoprolol works by selectively blocking beta-1 adrenergic receptors, which are predominantly found in cardiac tissue, thereby reducing heart rate, cardiac contractility, and blood pressure, as evidenced by the most recent and highest quality study 1. The mechanism of action of metoprolol involves the competitive blockade of the effects of catecholamines on cell membrane beta receptors, specifically beta-1 adrenergic receptors located primarily in the myocardium, as described in 1. When metoprolol binds to these receptors, it prevents catecholamines like epinephrine and norepinephrine from activating them, thereby inhibiting sympathetic nervous system stimulation of the heart. This selective blockade results in decreased heart rate, reduced cardiac contractility, and lowered blood pressure. By slowing the heart rate and reducing the force of contractions, metoprolol decreases myocardial oxygen demand, making it useful for treating conditions like hypertension, angina, heart failure, and post-myocardial infarction. The beta-1 selectivity of metoprolol is dose-dependent, meaning at higher doses it may lose some selectivity and affect beta-2 receptors in the lungs and blood vessels as well, as noted in 1. Metoprolol is typically administered at doses ranging from 25-100 mg twice daily for hypertension or 100-400 mg daily for angina, with dosing adjusted based on patient response. Unlike non-selective beta blockers, metoprolol's beta-1 selectivity reduces the risk of bronchospasm in patients with respiratory conditions, though caution is still warranted in those with severe asthma or COPD, as highlighted in 1. Some key points to consider when using metoprolol include:

• Its effectiveness in reducing anginal symptoms and ischemia, as shown in 1
• The importance of using beta-1 selective agents to minimize side effects and precautions, as discussed in 1 and 1
• The potential for additive effects when combined with other anti-anginal drugs, such as calcium channel blockers, as noted in 1

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 Clinical pharmacology studies have demonstrated the beta-blocking activity of metoprolol, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia

The mechanism of action of metoprolol is as a beta 1-selective adrenergic receptor blocker, which means it preferentially blocks beta 1-adrenergic receptors in the heart, reducing heart rate and cardiac output. At higher concentrations, it also inhibits beta 2-adrenoreceptors. The main effects of metoprolol include:

• Reduction in heart rate and cardiac output
• Reduction of systolic blood pressure upon exercise
• Inhibition of isoproterenol-induced tachycardia
• Reduction of reflex orthostatic tachycardia 2

From the Research

Mechanism of Action of Metoprolol

The mechanism of action of metoprolol, a beta-1 selective adrenergic receptor blocker, can be understood through its effects on the body's adrenergic receptors. Key points about its mechanism include:

• Metoprolol is a beta1-selective adrenoceptor blocking drug, which means it primarily affects the beta-1 adrenergic receptors in the heart 3.
• By blocking these receptors, metoprolol reduces the effects of epinephrine (adrenaline) and norepinephrine (noradrenaline) on the heart, leading to a decrease in heart rate and contractility 4.
• This reduction in heart rate and contractility decreases the oxygen demand of the heart, which is beneficial in conditions such as angina pectoris and hypertension 3, 5.
• Metoprolol also decreases plasma renin activity, which contributes to its antihypertensive effects 4.

Effects on Heart Failure

In the context of heart failure, metoprolol's mechanism of action is related to its ability to:

• Inhibit chronic beta-1 stimulation-induced myocardial apoptosis, necrosis, and inflammation, which can help reduce the progression of heart failure 6.
• Reduce the risk of death and hospitalization in patients with heart failure, as demonstrated in clinical trials 7, 6.

Pharmacological Properties

Metoprolol's pharmacological properties include:

• Beta-1 selectivity, which means it has a higher affinity for beta-1 receptors than for beta-2 receptors 3, 4.
• A long duration of action, making it suitable for twice-daily administration 3.
• Good tolerability, with common side effects including temporary fatigue, dizziness, and headache 5.