Description
Metoprolol (tartrate) (Item No. 21165) is an analytical reference standard categorized as a β
1-adrenergic receptor blocker.
1 This product is intended for use in analytical forensic applications. Metoprolol (succinate) is available as a general research tool (Item No.
15429).
Chemical Properties
White or almost white, crystalline powder or colourless crystals.
Originator
Betaloc,Astra,UK,1975
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.
