Chemical trapping of labile aldehyde intermediates in the metabolism of propranolol and oxprenolol.
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.
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D003641:Deamination; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D013058:Mass Spectrometry; D008930:Mitochondria, Liver / Q000378:metabolism; D010096:Oxprenolol / Q000378:metabolism*; D011433:Propranolol / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D010096:Oxprenolol; D011433:Propranolol