CHEMICAL TRAPPING OF LABILE ALDEHYDE INTERMEDIATES IN THE METABOLISM OF PROPRANOLOL AND OXPRENOLOL

  • 1 January 1981
    • journal article
    • research article
    • Vol. 34  (2) , 193-205
Abstract
Propranolol, a .beta.-antagonist, is N-dealkylated to N-desisopropylpropranolol (DIP) by rat liver microsomal enzymes. DIP was shown to be rapidly deaminated by monoamine oxidase (MAO). 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. 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 produced a labile aldehyde which could be trapped and identified as its O-methyloxime.