Biotransformation of Desoxypeganine by Microsomal Enzymes of the Rabbit Liver

✍ Scribed by Sascha Illgner; Rudolf Matusch

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 87 KB
• Volume: 338
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200400921

✦ Synopsis

Abstract

The biotransformation of the anticholinergic quinazoline alkaloid Desoxypeganine is studied by means of aerobic incubation with the non‐induced supernatant obtained at 9000g from rabbit liver homogenates as enzyme source followed by an admixture of NADPH. The metabolites were identified by highperformance liquid chromatography, chemical ionisation mass spectrometry (LC‐CI MS) and electron impact mass spectrometry (LC‐EI MS) in comparison with synthetic reference compounds and typical ion fragments taken from literature data. C‐oxidation of Desoxypeganine to the major metabolite Pegenone was observed as well as the hydroxylation of the alicyclic ring. The incubation mixture followed Michaelis‐Menten kinetics characterised by K~m~ = 5.8 × 10^—5^ mol L^—1^ and V~max~ = 4.32 nmol Pegenone/min per mg protein or 3.37 nmol Pegenone/min per nmol CYP 450, respectively. These in vitro results demonstrate that the bioactive substance Desoxypeganine is easily oxidised to its ineffective metabolite Pegenone. This provokes a problem for correct dosage finding in formulations for the treatment of Alzheimer' disease and in the therapy of alcoholism and nicotine dependence.