Metoprolol

Metoprolol

Clinical data
Trade names	Lopressor, Toprol-xl
AHFS/Drugs.com	Monograph
MedlinePlus	a682864
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Metoprolol
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral, IV
ATC code	C07AB02 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	12%
Metabolism	Hepatic via CYP2D6, CYP3A4
Elimination half-life	3-7 hours
Excretion	Renal
Identifiers
IUPAC name (RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
CAS Number	51384-51-1 Y
PubChem CID	4171
IUPHAR/BPS	553
DrugBank	DB00264 Y
ChemSpider	4027 Y
UNII	GEB06NHM23
KEGG	D02358 Y
ChEBI	CHEBI:6904 Y
ChEMBL	ChEMBL13 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H25NO3
Molar mass	267.364 g/mol
3D model (JSmol)	Interactive image
Melting point	120 °C (248 °F)
SMILES O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
InChI InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3 Y Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N Y
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Metoprolol

Clinical data
Trade names	Lopressor, Toprol-xl
AHFS/Drugs.com	Monograph
MedlinePlus	a682864
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Metoprolol
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral, IV
ATC code	C07AB02 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	12%
Metabolism	Hepatic via CYP2D6, CYP3A4
Elimination half-life	3-7 hours
Excretion	Renal
Identifiers
IUPAC name (RS)-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
CAS Number	51384-51-1 Y
PubChem CID	4171
IUPHAR/BPS	553
DrugBank	DB00264 Y
ChemSpider	4027 Y
UNII	GEB06NHM23
KEGG	D02358 Y
ChEBI	CHEBI:6904 Y
ChEMBL	ChEMBL13 Y
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C15H25NO3
Molar mass	267.364 g/mol
3D model (JSmol)	Interactive image
Melting point	120 °C (248 °F)
SMILES O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
InChI InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3 Y Key:IUBSYMUCCVWXPE-UHFFFAOYSA-N Y
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

For patient information, click here.

Synonyms / Brand Names: Lopressor^®, Toprol XL^®

Overview

Metoprolol (/mɛˈtoʊproʊlɑːl/, /mɛtoʊˈproʊlɑːl/) is a selective β₁ receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or as metoprolol tartrate (where 100 mg metoprolol tartrate corresponds to 95 mg metoprolol succinate). The tartrate is an immediate-release and the succinate is an extended-release formulation.

Category

Beta-blockers, Antimigraine drugs

FDA Package Insert

LOPRESSOR (metoprolol tartrate) tablet

Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Medical uses

Metoprolol is used for a number of conditions including: hypertension, angina, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, congestive heart failure, and prevention of migraine headaches.

• Treatment of heart failure.
• Vasovagal syncope
• Adjunct in treatment of hyperthyroidism
• Long QT syndrome, especially for patients with asthma, as metoprolol's β1 selectivity tends to interfere less with asthma drugs, which are often β2-adrenergic receptor-agonist drugs

Due to its selectivity in blocking the beta₁ receptors in the heart, metoprolol is also prescribed for off-label use in performance anxiety, social anxiety disorder, and other anxiety disorders.

Adverse effects

Side-effects, especially with higher dosages, include the following: dizziness, drowsiness, fatigue, diarrhea, unusual dreams, ataxia, trouble sleeping, depression, and vision problems. It may also reduce blood flow to the hands and feet, causing them to feel numb and cold; smoking may worsen this effect. 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 and vivid dreams and nightmares.

Serious side-effects that are advised to be reported immediately include, but are not limited to, symptoms of bradycardia (a very slow heartbeat (less than 50 bpm)), persistent symptoms of dizziness, fainting and unusual fatigue, bluish discoloration of the fingers and toes, numbness/tingling/swelling of the hands or feet, sexual dysfunction, erectile dysfunction (impotence), hair loss, mental/mood changes, depression, trouble breathing, cough, dyslipidemia, and increased thirst. Other highly unlikely symptoms include easy bruising or bleeding, persistent sore throat or fever, yellowing skin or eyes, stomach pain, dark urine, and persistent nausea. Symptoms of an allergic reaction include: rash, itching, swelling, and severe dizziness. Taking it with alcohol might cause mild body rashes and therefore is not recommended.

Precautions

Metoprolol may worsen the symptoms of heart failure in some patients, who may experience chest pain or discomfort; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; shortness of breath; swelling of the face, fingers, feet, or lower legs; weight gain; or wheezing.

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

This medicine may cause some people to become less alert than they are normally, making it dangerous for them to drive, use machines, or do other things.

Overdosage

Excessive doses of Metoprolol can cause severe hypotension, bradycardia, metabolic acidosis, seizures and cardiorespiratory arrest. Blood or plasma concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 200 μg/L during therapeutic administration, but can range from 1–20 mg/L in overdose victims.

Physical properties

Metoprolol has a very low melting point, tartrate around 120°C, succinate around 136°C. Because of this, metoprolol is always manufactured in a salt-based solution, as drugs with low melting points are difficult to work with in a manufacturing environment. The free base exists as a waxy white solid, and the tartrate salt is finer crystalline material.

Metabolism

Metoprolol undergoes a-hydroxylation and O-demethylation as a substrate of the cytochrome liver enzymes CYP2D6 and a small percentage by CYP3A4.

Pharmacology

• Selective
• Moderately lipophilic
• Without intrinsic sympathomimetic activity (ISA)
• With weak membrane stabilizing activity
• Short half-life, therefore must be taken at least twice daily or as a slow-release preparation
• Decreases heart rate, contractility and cardiac output, therefore decreasing blood pressure
• Metabolized in the liver to inactive metabolite

Chemistry

Metoprolol, 1-(iso-propylamino)-3-[4′(2-methoxyethyl)phenoxy]-2-propanol, is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorohydrin in the presence of a base, isolating 1,2-epoxy-3-[4′(2-methoxyethyl)phenoxy]propane, the subsequent reaction with isopropylamine, gives an opening of the epoxide ring and leads to the formation of metoprolol.

• P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, B. A. H. Ablad, A. E. Brandstrom, Template:US Patent (1975).
• A. E. Brandstrom, P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, DE 2106209  (1971).

Brand names

Amlong MT combination of Amlodipine and Metoprolol with 25 and 50 mg claim for Metoproplol(Micro Labs-India)

Toprol XL 50 mg

It is marketed under the brand name Lopressor by Novartis, and Toprol-XL (in the USA); Selokeen (in the Netherlands); as Minax by Alphapharm (in Australia), Metrol by Arrow Pharmaceuticals (in Australia), as Betaloc by AstraZeneca, as Bloxan by Krka (company) (in Slovenia), as Neobloc by Unipharm (in Israel), Presolol by Hemofarm (in Serbia) and as Corvitol by Berlin-Chemie AG (in Germany). In India, this drug is available under the brand names of Met-XL, Metolar and Starpress,Restopress. A number of generic products are available as well.

Mechanism of Action

Metoprolol is a beta1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature.