56392-17-7

Basic information

• Product Name: (+-)metoprolol-(+)tartrate
• Synonyms: Metoprolol Tartrate; Metoproloe Tartrate
• CAS NO: 56392-17-7
• Molecular Formula: C₄H₆O₆*C₁₅H₂₅NO₃
• Molecular Weight: 684.81
• EINECS: 260-148-9
• Product Categories: Cardiovascular;Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Adrenoceptor;Cardiovascular APIs;UROXATRAL
• Mol File: 56392-17-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 120℃
• Boiling Point: 695.37°C (rough estimate)
• Flash Point: 9℃
• Density: 1.1946 (rough estimate)
• Refractive Index: 1.5300 (estimate)
• Storage Temp.: Desiccate at RT
• Solubility: H2O: soluble50mg/mL
• Water Solubility: Soluble in water (>1000 mg/ml), methanol (>500 mg/ml), chloroform (496 mg/ml), ethanol (31 mg/ml at 25°C), and DMSO (100 mg/ml at 25°C).
• Stability: Stable. Incompatible with strong oxidizing agents.
• Merck: 14,6151
• CAS DataBase Reference: (+-)metoprolol-(+)tartrate(CAS DataBase Reference)
• NIST Chemistry Reference: (+-)metoprolol-(+)tartrate(56392-17-7)
• EPA Substance Registry System: (+-)metoprolol-(+)tartrate(56392-17-7)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 7-16-36/37-45-24/25
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 3
• RTECS: UB7450100
• Hazardous Substances Data: 56392-17-7(Hazardous Substances Data)

Usage

Description

(+-)metoprolol-(+)tartrate, also known as metoprolol tartrate, is a certified solution standard used in clinical toxicology or forensic analysis by LC-MS/MS or GC/MS. It is a β1-adrenergic receptor blocker, which is a white or almost white, crystalline powder or colorless crystals. Metoprolol tartrate is used for the treatment of multiple heart conditions, including hypertension, angina, and tachycardia. It is sold under the trade names Lepressor and Toprol XL.

Uses

Used in Pharmaceutical Industry:
(+-)metoprolol-(+)tartrate is used as an antihypertensive, antianginal, and antiarrhythmic (class II) agent for the treatment of a variety of cardiovascular disorders. It acts as a β1 selective aryloxypropanolamine andrenergic antagonist, which helps in managing hypertension, angina, and tachycardia.
Used in Analytical Forensic Applications:
(+-)metoprolol-(+)tartrate is used as an analytical reference standard for forensic analysis, aiding in the identification and quantification of the compound in various samples.
Used in Clinical Toxicology:
(+-)metoprolol-(+)tartrate is used as a certified solution standard in clinical toxicology, helping in the diagnosis and treatment of poisoning cases involving this compound.
Used in Research and Development:
(+-)metoprolol-(+)tartrate is used as a general research tool for the development of new drugs and therapies related to cardiovascular disorders and other conditions that can be treated with β1-adrenergic receptor blockers.
Used in Treatment of Heart Conditions:
(+-)metoprolol-(+)tartrate is used as a β1-adrenergic blocker for the treatment of multiple heart conditions, such as hypertension, angina, and tachycardia. It inhibits spontaneous endothelin-1 production in vitro and displays antihypertensive and antianginal activity in vivo.
Used as an alpha(1)-adrenergic blocker:
(+-)metoprolol-(+)tartrate is used as an alpha(1)-adrenergic blocker, which helps in the management of certain cardiovascular conditions by blocking the action of adrenaline on alpha(1)-adrenergic receptors.

β1 receptor blocker

Metoprolol tartrate is a selective β1-adrenergic receptor blocker,oral absorption is rapid? and complete,it is used for the treatment of hypertension, angina pectoris, myocardial infarction, hypertrophic cardiomyopathy, aortic dissection, cardiac arrhythmia, hyperthyroidism, cardiac neurosis and other diseases. In recent years, it is also used for ther treatment of heart failure, which can reduce mortality. In unstable/non-ST-segment elevation myocardial infarction and acute myocardial infarction? control guiding principles developed by American Heart Association , effect of metoprolol tartrateare is clearly recognized. In the past, concerns about β-blocker therapy caused hypotension is too large, and for the consideration that there may be racial differences between Asians in β-blocker use and the West, patients with treatment of β-blockers in China is? fewer? , the use of β-blockers is in lower dose. Metoprolol tartrate has a weaker membrane stability and it has no intrinsic sympathomimetic activity, and in comparison with similar drugs commonly used in clinical propranolol ,in addition to the advantages of β1-blocker on its pharmacodynamic,it also has its pharmacokinetic kinetics? advantages, such as relatively weak first-pass effect compared with propranolol, simple metabolic pathways, most pharmacologically inactive metabolites and the like.

Hazards & Safety Information

Category: toxic substances Toxicity grading: Middle? poisoning Acute toxicity: oral?-rat LD50: 5500 mg/kg; Oral-Mouse LD50: 1500 mg/kg Flammability and hazard characteristics: It is combustible; fire decomposition produces toxic nitrogen oxide gases Storage Characteristics: Ventilated, low-temperature ,dry storeroom. Extinguishing agent: Water, carbon dioxide, dry powder, sandy soil.

Therapeutic Function

Beta-adrenergic blocker

Biological Activity

Selective β 1 -adrenoceptor antagonist (K i values are 47, 2960 and 10100 nM for β 1 , β 2 and β 3 adrenoceptors respectively). Inhibits spontaneous endothelin-1 production in vitro and displays antihypertensive and antianginal activity in vivo .

Clinical Use

Beta-adrenoceptor blocker: Hypertension Angina Cardiac arrhythmias Migraine prophylaxis Hyperthyroidism

Veterinary Drugs and Treatments

Because metoprolol is relatively safe to use in animals with bronchospastic disease, it is often chosen over propranolol. It may be effective in supraventricular tachyarrhythmias, premature ventricular contractions (PVC’s, VPC’s), systemic hypertension, and treating cats with hypertrophic cardiomyopathy. There is increasing interest in using beta blockers in heart failure in dogs; one retrospective study showed increased survival times when dogs were given metoprolol, but definitive prospective, double-blinded studies have not been reported documenting the benefit (increased survival) of beta-blockers in dogs with heart failure.

Drug interactions

Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide; concentration increased by propafenone and dronedarone. Antibacterials: concentration reduced by rifampicin. Antidepressants: enhanced hypotensive effect with MAOIs; concentration increased by citalopram and escitalopram and possibly by paroxetine - avoid. Antihypertensives; enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin. Antimalarials: increased risk of bradycardia with mefloquine; avoid with artemether/lumefantrine. Antipsychotics enhanced hypotensive effect with phenothiazines. Antivirals: avoid concomitant use with tipranavir in heart failure. Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil. Cytotoxics: possible increased risk of bradycardia with crizotinib. Diuretics: enhanced hypotensive effect. Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension.

Metabolism

Extensively metabolised in the liver, mainly by the cytochrome P450 isoenzyme CYP2D6, and undergoes oxidative deamination, O-dealkylation followed by oxidation, and aliphatic hydroxylation. The metabolites are excreted in the urine with only small amounts of unchanged metoprolol.

Upstream product

• 56718-71-9 4-(2-methoxyethyl)phenol 
• 51384-51-1 (RS)-metoprolol 
• 87-69-4 tartaric acid 

Downstream Products

• 138768-62-4 N-nitrosometoprolol 
• 1251957-60-4 C₁₅H₂₄⁽¹²⁵⁾INO₃ 
• 56718-78-6 3-isopropyl-5-((4-(2-methoxyethyl)phenoxy)methyl)oxazolidin-2-one 

Relevant articles and documents

COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SALT SENSITIVITY OF BLOOD PRESSURE

To characterize the urinary exosome miRNome, microarrays were used to identify the miRNA spectrum present within urinary exosomes from ten individuals that were previously classified for their salt sensitivity status. The present application discloses distinct patterns of selected exosomal miRNA expression that were different between salt-sensitive (SS), salt-resistant (SR), and inverse salt-sensitive (ISS) individuals. These miRNAs can be useful as biomarkers either individually or as panels comprising multiple miRNAs. The present invention provides compositions and methods for identifying, diagnosing, monitoring, and treating subjects with salt sensitivity of blood pressure. The applications discloses panels of miRNAs useful for comparing profiles, and in some cases one or more of the miRNAs in a panel can be used. The miRNAs useful for distinguishing SS and SR or ISS and SR subjects. One or more of the 45 miRNAs can be used. Some of the miRNAs have not been previously reported to be circulating. See those miRNAs with asterisks in FIG. 1 and below. The present invention encompasses the use of one or more of these markers for identifying and diagnosing SR, SS, and ISS subjects.

Metoprolol manufacturing process

Metoprolol manufacturing process with optimized reaction temperatures and reactant molar ratios, to avoid the manufacture of excessive epoxide intermediates, thus avoiding the need for purification of epoxide intermediates, thus achieving higher yields and higher-purity product than that seen in the prior art teachings.