Metoprolol tartrate Property

Melting point:

120℃

Boiling point:

695.37°C (rough estimate)

Density 

1.1946 (rough estimate)

refractive index 

1.5300 (estimate)

Flash point:

9℃

storage temp. 

2-8°C

solubility 

H2O: soluble50mg/mL

form 

powder

color 

white to off-white

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).

λmax

223nm(H2O)(lit.)

Merck 

14,6151

BCS Class

1

Stability:

Stable. Incompatible with strong oxidizing agents.

CAS DataBase Reference

56392-17-7(CAS DataBase Reference)

Safety

Hazard Codes 

F,T

Risk 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

HS Code 

29225090

Toxicity

LD50 in female mice, male rats (mg/kg): 118, ~90 i.v.; 2090, 3090 orally (Bodin)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H411Toxic to aquatic life with long lasting effects

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P308+P313IF exposed or concerned: Get medical advice/attention.

P391Collect spillage. Hazardous to the aquatic environment

Metoprolol tartrate Chemical Properties,Usage,Production

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.

Uses

Hypertensive medication.

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.

Description

Metoprolol (tartrate) (Item No. 21165) is an analytical reference standard categorized as a β₁-adrenergic receptor blocker. This product is intended for use in analytical forensic applications. Metoprolol (succinate) is available as a general research tool .

Chemical Properties

White or almost white, crystalline powder or colourless crystals.

Originator

Betaloc,Astra,UK,1975

Uses

Metoprolol tartrate is an antagonist of the β1-AR (β1-adrenoceptor). It inhibits spontaneous endothelin-1 production in vitro and displays antihypertensive and antianginal activity in vivo.

Uses

A ? selective aryloxypropanolamine andrenergic antagonist. Used in the treatment of a variety of cardiovascular disorder. Antihypertensive; antianginal; antiarrhythmic (class II)

Uses

A β1 selective aryloxypropanolamine andrenergic antagonist. Used in the treatment of a variety of cardiovascular disorder. Antihypertensive; antianginal; antiarrhythmic (class II).

Uses

alpha(1)-adrenergic blocker

Uses

A b1-Adrenergic blocker

Manufacturing Process

The starting material 1,2-epoxy-3-[p-(β-methoxyethyl)phenoxy]-propane was obtained from p-(β-methoxyethyl)-phenol which was reacted with epichlorohydrin whereafter the reaction product was distilled at 118°C to 128°C at a pressure of 0.35mm Hg.
1,2-Epoxy-3-[p-(β-methoxyethyl)-phenoxy]-propane (16.7g) was dissolved in 50 ml isopropanol and mixed with 20 ml isopropylamine. The mixture was heated in an autoclave on boiling water-bath overnight, whereafter it was evaporated and the remainder dissolved in 2 N HCI. The solution was extracted first with ether and thereafter with methylene chloride. After evaporating the methylene chloride phase, the hydrochloride of 1- isopropylamino-3-[p(β-methoxyethyl)-phenoxy] -propanol-2 was obtained which, after recrystallization from ethyl acetate, weighed 10.4 g. Melting point 83°C. Equivalent weight: found 304.0, calculated 303.8.
The hydrochloride is then converted to the tartrate.

brand name

Lopressor (Novartis).

Therapeutic Function

Beta-adrenergic blocker

General Description

A certified solution standard applicable for use in clinical toxicology or forensic analysis by LC-MS/MS or GC/MS. Metoprolol is used for the treatment of multiple heart conditions including hypertension, angina, and tachycardia. This beta blocker is sold under the trade names Lepressor and Toprol XL^?.

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.

storage

Desiccate at RT