Chemical Properties
White or almost white, slightly hygroscopic, crystalline powder.
Uses
Beta2-adrenoceptor agonist; bronchodilator.
Uses
Bronchodilatator;Beta-adrenergic agonist
Brand name
Alupent (Boehringer Ingelheim); Prometa (Muro).
Originator
Alupent, Boehringer Ingelheim ,W. Germany ,1961
Manufacturing Process
In an initial operation, 3,5-diacetoxyacetophenone was reacted first with
bromine and then with isopropylamine to give 1-(3,5-dihydroxyphenyl)-2-
isopropylaminoethanone.
59 g of 1-(3,5-dihydroxy-phenyl)-2-isopropylaminoethanone (free base) were
dissolved in 590 cc of methanol, and the solution was hydrogenated in the
presence of about 80 g Raney nickel at room temperature and under a
pressure of 5 atm. Hydrogen absorption was terminated after a few minutes.
The catalyst was separated by vacuum filtration, and the filtrate, an ethanolic
solution of 1-(3,5-dihydroxyphenyl)-1-hydroxy-2-isopropylaminoethane, was
admixed with the calculated amount of an alcoholic 20% sulfuric acid solution.
A crystalline precipitate formed which was filtered off and washed with
alcohol. For purification, the product was dissolved in water and the solution
was filtered through iron-free charcoal.
Thereafter, the filtrate was evaporated to dryness in vacuo and the residue
was taken up in alcohol. The crystalline precipitate which separated out after
some standing was separated by vacuum filtration and washed with alcohol.
After recrystallization from 90% alcohol, 61 g (83.2% of theory) of 1-(3,5-
dihydroxyphenyl)-1-hydroxy-2-isopropylamino-ethane sulfate, MP 202° to
203°C, was obtained.
Therapeutic Function
Bronchodilator
Pharmacokinetics
Metaproterenol is a direct-acting resorcinol analogue of isoproterenol. The N-isopropyl is
β-directing, and the combination with the resorcinol ring system enhances the selectivity for the
β2-receptors. It is the least potent of the β2-selective agonists, however, most likely because of
the poor β2-selectivity of the isopropyl group. It has good oral bioavailability being resistant to
COMT and only slowly metabolized by MAO. When administered orally, it has an onset of
approximately 30 minutes with a 4-hour duration. Inhaled metaproterenol can have an onset as
quick as 5 minutes; however, it can be as long as 30 minutes in susceptible individuals.
Metaproterenol is available in tablet, syrup, and inhalation dosage forms and is recommended for
bronchial asthma attacks and treatment of acute asthmatic attacks in children 6 years of age and
older (5% solution for inhalation only). Metaproterenol has the same adverse effect profile as
other adrenergic agonists, but with a decreased incidence of arrhythmias.
