<!-- Definition and medical uses -->

Metoprolol, sold under the brand names Lopressor and Toprol-XL among others, is a medication used to treat angina, high blood pressure and a number of conditions involving an abnormally fast heart rate. Risk in pregnancy has not been ruled out. It appears to be safe in breastfeeding. The metabolism of metoprolol can vary widely among patients, often as a result of hepatic impairment or CYP2D6 polymorphism.

<!-- History, Society and Culture -->

Metoprolol was first made in 1969, patented in 1970, and approved for medical use in 1978. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication.

Medical uses

Metoprolol is used for a number of conditions, including angina, acute myocardial infarction, high blood pressure, supraventricular tachycardia, ventricular tachycardia, congestive heart failure, and prevention of migraine headaches. Both oral and intravenous forms of metoprolol are available for administration. The different salt versions of metoprolol – metoprolol tartrate and metoprolol succinate – are approved for different conditions and are not interchangeable.

Off-label uses include supraventricular tachycardia and thyroid storm. Metoprolol may also cause the hands and feet to feel cold. Due to the high penetration across the blood–brain barrier, lipophilic beta blockers such as propranolol and metoprolol are more likely than other less lipophilic beta blockers to cause sleep disturbances such as insomnia, vivid dreams and nightmares. Patients should be cautious while driving or operating machinery due to its potential to cause decreased alertness.

There may also be an impact on blood sugar levels, and it can potentially mask signs of low blood sugar.

Precautions

Metoprolol succinate controlled release (CR)/extended release (XR) plays an important role in the management of Heart Failure with reduced Ejection Fraction (HFrEF) defined by a left ventricular ejection fraction of ≤ 40%. Evidence supports it reduces the incidence of hospitalisation due to cardiovascular events and worsening heart failure when used in combination with other medications in accordance to current prescribing guidelines. Initiating metoprolol in patients with severe heart failure may cause early clinical deterioration and may not be beneficial in some cases, however, MERIT-HF showed that by approximately two months metoprolol reduces mortality and hospitalisations. COMET suggests early mortality risk is more strongly linked to beta-blocker dose reduction or withdrawal during decompensated heart failure, rather than metoprolol initiation itself.. Patients should monitor for swelling of extremities, fatigue, and shortness of breath..

Given that the evidence from the Cochrane Review there is some efficacy of metoprolol as a prevention of atrial fibrillation recurrence but not prominent. Further investigation may require assessing the ongoing benefit.

This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.

Pharmacology

Mechanism of action

Metoprolol is a beta blocker, or an antagonist of the β-adrenergic receptors. It is specifically a selective antagonist of the β<sub>1</sub>-adrenergic receptor and has no intrinsic sympathomimetic activity. It also suppresses the norepinephrine-induced increase in the sarcoplasmic reticulum (SR) Ca<sup>2+</sup> leak and the spontaneous SR Ca<sup>2+</sup> release, which are the major triggers for atrial fibrillation.

Pharmacokinetics

Metoprolol is mostly absorbed from the intestine with an absorption fraction of 0.95. The systemic bioavailability after oral administration is approximately 50%. More lipophilic beta blockers tend to cross the blood–brain barrier more readily, with greater potential for effects in the central nervous system as well as associated neuropsychiatric side effects. For comparison, the brain-to-blood ratio of the highly lipophilic propranolol was 15:1 to 26:1 and of the hydrophilic atenolol was 0.2:1.

Stereochemistry

Metoprolol contains a stereocenter and consists of two enantiomers. This is a racemate, i.e. a 1:1 mixture of (R)- and the (S)-form:

{| class="wikitable" style="text-align:center"

|- class="hintergrundfarbe6"

! colspan="2"| Enantiomers of metoprolol

|-

| class=skin-invert-image|300 px<br /><small> CAS-Number: 81024-43-3</small>

| class=skin-invert-image|300 px<br /><small> CAS-Number: 81024-42-2</small>

|}

Formulations

Metoprolol was synthesized and its activity discovered in 1969.

Metoprolol tartrate was first developed by Novartis and this dosage form received approval in the US in 1978. The extended-release salt, metoprolol succinate was developed by Astra Pharmaceuticals, and received a US patent in 1992.

Society and culture

Metoprolol was approved for medical use in the United States in August 1978.

Sports

Because beta blockers can be used to reduce heart rate and minimize tremors, which can enhance performance in sports such as archery, metoprolol is banned by the world anti-doping agency in some sports.