Chemical trapping of labile aldehyde intermediates in the metabolism of propranolol and oxprenolol

Res Commun Chem Pathol Pharmacol. 1981 Nov;34(2):193-205.

Abstract

Propranolol is N-dealkylated to N-desisopropylpropranolol (DIP) by microsomal enzymes. DIP was shown in this study to be rapidly deaminated by monoamine oxidase (MAO). Thus, incubation of DIP (10(-4) M) with rat liver mitochondria for 90 min demonstrated 74.8 +/- 4.1% metabolism which was almost completely blocked by the MAO inhibitor pargyline (10(-5) M). The end products of this deamination were 3-(alpha-naphthoxy)-1,2-propylene glycol (Glycol) and 3-(alpha-naphthoxy)lactic acid (NLA). In the presence of excess NADH the Glycol was the major product whereas NLA was the major product in the presence of excess NAD+. The intermediate aldehyde in this deamination reaction, 3-(alpha-naphthoxy)-2-hydroxypropanal (Ald), was extremely labile and decomposed quantitatively to alpha-naphthol when removed from the incubates. However, the addition of methoxyamine hydrochloride directly to the incubates made it possible to chemically trap the intact Ald as an O-methyloxime and prove its structure by gas chromatography-mass spectrometry. The deamination of the primary amine of oxprenolol also gave rise to a labile aldehyde which could be trapped and identified as its O-methyloxime.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehydes / metabolism*
  • Animals
  • Deamination
  • Gas Chromatography-Mass Spectrometry
  • Male
  • Mass Spectrometry
  • Mitochondria, Liver / metabolism
  • Oxprenolol / metabolism*
  • Propranolol / metabolism*
  • Rats
  • Rats, Inbred Strains

Substances

  • Aldehydes
  • Oxprenolol
  • Propranolol