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| {{Metoprolol}}{{Drugbox | | {{Details0|Metoprolol succinate (tablet)}} |
| | verifiedrevid = 459444186
| | {{Details0|Metoprolol tartrate (injection)}} |
| | IUPAC_name = (''RS'')-1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
| | {{Details0|Metoprolol tartrate (tablet)}} |
| | image = | |
| | imagename = 1 : 1 mixture (racemate)
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| | drug_name = Metoprolol
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| <!--Clinical data-->
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| | tradename = Lopressor, Toprol-xl
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| | Drugs.com = {{drugs.com|monograph|metoprolol-succinate}}
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| | MedlinePlus = a682864
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| | licence_US = Metoprolol
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| | pregnancy_AU = C
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| | pregnancy_US = C
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| | legal_status = Rx-only
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| | routes_of_administration = Oral, [[Intravenous|IV]]
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| <!--Pharmacokinetic data-->
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| | bioavailability = 12%
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| | metabolism = [[Liver|Hepatic]] via [[CYP2D6]], [[CYP3A4]]
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| | elimination_half-life = 3-7 hours
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| | excretion = [[Kidney|Renal]]
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| <!--Identifiers-->
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| | CAS_number_Ref = {{cascite|correct|??}}
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| | CAS_number = 51384-51-1
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| | ATC_prefix = C07
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| | ATC_suffix = AB02
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| | PubChem = 4171
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| | IUPHAR_ligand = 553
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| | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| | DrugBank = DB00264
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| | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| | ChemSpiderID = 4027
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| | UNII_Ref = {{fdacite|correct|FDA}}
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| | UNII = GEB06NHM23
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| | KEGG_Ref = {{keggcite|correct|kegg}}
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| | KEGG = D02358
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| | ChEBI_Ref = {{ebicite|correct|EBI}}
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| | ChEBI = 6904
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| | ChEMBL_Ref = {{ebicite|correct|EBI}}
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| | ChEMBL = 13
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| <!--Chemical data-->
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| | C=15 | H=25 | N=1 | O=3
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| | molecular_weight = 267.364 [[gram|g]]/[[Mole (unit)|mol]]
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| | smiles = O(c1ccc(cc1)CCOC)CC(O)CNC(C)C
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| | InChI = 1/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
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| | InChIKey = IUBSYMUCCVWXPE-UHFFFAOYAN
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| | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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| | StdInChI = 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
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| | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
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| | StdInChIKey = IUBSYMUCCVWXPE-UHFFFAOYSA-N
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| | melting_point = 120
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| }}
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| __NOTOC__
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| {{CMG}}; {{AE}} {{AZ}}
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| '''''For patient information, click [[Metoprolol (patient information)|here]].'''''
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| {{SB}} Lopressor<sup>®</sup>, Toprol XL<sup>®</sup>
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| ==Overview==
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| '''Metoprolol''' ({{IPAc-en|m|ɛ|ˈ|t|oʊ|p|r|oʊ|l|ɑː|l}}, {{IPAc-en|m|ɛ|t|oʊ|'|p|r|oʊ|l|ɑː|l}}) is a selective [[beta blocker|β<sub>1</sub> receptor blocker]] used in treatment of several diseases of the cardiovascular system, especially [[hypertension]]. The active substance metoprolol is employed either as ''metoprolol [[succinic acid|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 [[Pharmaceutical formulation|formulation]].<ref>{{cite journal | author = Cupp M | title = Alternatives for Metoprolol Succinate | journal = Pharmacist's Letter / Prescriber's Letter | year = 2009 | volume = 25 | issue = 250302 | url = http://www.ncbop.org/PDF/MetoprololShortageMarch2009.pdf | format = pdf | accessdate = 2012-07-06 }}</ref>
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| ==Category==
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| Beta-blockers, Antimigraine drugs
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| ==FDA Package Insert==
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| ====LOPRESSOR (metoprolol tartrate) tablet====
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| ''' [[Metoprolol indications and usage|Indications and Usage]]'''
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| '''| [[Metoprolol dosage and administration|Dosage and Administration]]'''
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| '''| [[Metoprolol dosage forms and strengths|Dosage Forms and Strengths]]'''
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| '''| [[Metoprolol contraindications|Contraindications]]'''
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| '''| [[Metoprolol warnings and precautions|Warnings and Precautions]]'''
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| '''| [[Metoprolol adverse reactions|Adverse Reactions]]'''
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| '''| [[Metoprolol drug interactions|Drug Interactions]]'''
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| '''| [[Metoprolol use in specific populations|Use in Specific Populations]]'''
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| '''| [[Metoprolol overdosage|Overdosage]]'''
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| '''| [[Metoprolol description|Description]]'''
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| '''| [[Metoprolol clinical pharmacology|Clinical Pharmacology]]'''
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| '''| [[Metoprolol nonclinical toxicology|Nonclinical Toxicology]]'''
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| '''| [[Metoprolol clinical studies|Clinical Studies]]'''
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| '''| [[Metoprolol how supplied storage and handling|How Supplied/Storage and Handling]]'''
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| '''| [[Metoprolol patient counseling information|Patient Counseling Information]]'''
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| '''| [[Metoprolol labels and packages|Labels and Packages]]'''
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| ==Medical uses==
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| 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]].<ref name=AHFS>{{cite web | title = Metoprolol | url = http://www.drugs.com/monograph/metoprolol-succinate.html | work = The American Society of Health-System Pharmacists | accessdate = 3 April 2011 }}</ref>
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| * Treatment of [[heart failure]].<!--
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| --><ref name="Lancet-MERIT-HF">{{cite journal | author = MERIT-HF Study Group | title = Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) | journal = Lancet | volume = 353 | issue = 9169 | pages = 2001–2007 | year = 1999 | pmid = 10376614| doi = 10.1016/S0140-6736(99)04440-2 }}</ref>
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| * [[Vasovagal syncope]]<ref name="pmid18376348">{{cite journal | author = Zhang Q, Jin H, Wang L, Chen J, Tang C, Du J | title = Randomized comparison of metoprolol versus conventional treatment in preventing recurrence of vasovagal syncope in children and adolescents | journal = Medical Science Monitor | volume = 14 | issue = 4 | pages = CR199–CR203 | year = 2008 | pmid = 18376348 |doi= |url = http://www.medscimonit.com/fulltxt.php?ICID=850297 }}</ref>
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| * Adjunct in treatment of [[hyperthyroidism]]
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| * [[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{{Citation needed|date=April 2011}}
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| Due to its selectivity in blocking the [[Beta-1 adrenergic receptor|beta<sub>1</sub>]] receptors in the heart, metoprolol is also prescribed for [[off-label use]] in [[performance anxiety]], [[social anxiety disorder]], and other [[anxiety disorder]]s.
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| ==Adverse effects==
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| 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.<ref name="drugs">{{ cite web | url = http://www.drugs.com/metoprolol.html | title = Metoprolol | publisher = Drugs.com }}</ref> 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.<ref name="pmid21180298">{{ cite journal | author = Cruickshank JM | title = Beta-blockers and heart failure | journal = Indian Heart Journal | year = 2010 | volume = 62 | issue = 2 | pages = 101–110 | pmid = 21180298 }}</ref>
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| 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.<ref name="drugs"/>
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| ===Precautions===
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| 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.<ref name="mayoclinic">{{ cite web | publisher = Mayo Clinic | work = Drug Information | url = http://www.mayoclinic.com/health/drug-information/DR602483/DSECTION=precautions- | title = Metoprolol (Oral Route) Precautions }}</ref>
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| This medicine may cause changes in blood sugar levels or cover up signs of low blood sugar, such as a rapid pulse rate.<ref name="mayoclinic" />
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| 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.<ref name="mayoclinic" />
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| ===Overdosage===
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| 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.<ref>{{ cite journal | author = Page C, Hacket LP, Isbister GK | title = The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: a case report | journal = Journal of Medical Toxicology | year = 2009 | volume = 5 | issue = 3 | pages = 139–143 | pmid = 19655287 }}</ref><ref>{{ cite journal | author = Albers S, Elshoff JP, Völker C, Richter A, Läer S | title = HPLC quantification of metoprolol with solid-phase extraction for the drug monitoring of pediatric patients | journal = Biomedical Chromatography | volume = 19 | issue = 3 | pages = 202–207 | year = 2005 | pmid = 15484221 | doi=10.1002/bmc.436}}</ref><ref>{{ cite book | author = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | year = 2008 | pages = 1023–1025 }}</ref>
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| ==Physical properties==
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| 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. | |
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| ==Metabolism==
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| Metoprolol undergoes a-hydroxylation and O-demethylation as a [[enzyme substrate|substrate]] of the cytochrome liver enzymes [[CYP2D6]] <ref>{{ cite journal | author = Swaisland HC, Ranson M, Smith RP, Leadbetter J, Laight A, McKillop D, Wild MJ | title = Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol | journal = Clinical Pharmacokinetics | year = 2005 | volume = 44 | issue = 10 | pages = 1067–1081 | pmid = 16176119 }}</ref> and a small percentage by [[CYP3A4]].
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| ==Pharmacology==
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| * Selective
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| * Moderately [[lipophilic]]
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| * Without intrinsic [[sympathomimetic]] activity (ISA)
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| * With weak membrane stabilizing activity
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| * Short [[Elimination half-life|half-life]], therefore must be taken at least twice daily or as a [[slow-release]] preparation
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| * Decreases heart rate, contractility and cardiac output, therefore decreasing blood pressure
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| * Metabolized in the liver to inactive metabolite
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| ==Chemistry==
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| 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.
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| *P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, B. A. H. Ablad, A. E. Brandstrom, {{US Patent|3873600}} (1975).
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| *A. E. Brandstrom, P. A. E. Carlsson, S. A. I. Carlsson, H. R. Corrodi, L. Ek, {{Cite patent|DE|2106209}} (1971).
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| ==Brand names==
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| Amlong MT combination of Amlodipine and Metoprolol with 25 and 50 mg claim for Metoproplol(Micro Labs-India)[[Image:ToprolXL50mg.png|thumb|50px|Toprol XL 50 mg]]
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| 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 drug|generic]] products are available as well.
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| ==Mechanism of Action==
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| ==References==
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| {{Reflist|2}}
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| [[Category:Drugs]]
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| [[Category:Antimigraine drugs]]
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| [[Category:Beta blockers]]
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