Species variability in the stereoselective N-oxidation of pargyline.
The monoamine oxidase inhibitor pargyline (N-benzyl-N-methyl-2-propynylamine) is known to undergo extensive in vitro microsomal N-oxidation, thought to be mediated predominantly by the flavin-containing monooxygenase (FMO) enzyme system. Formation of the pargyline N-oxide (PNO) metabolite creates a chiral nitrogen centre and thus asymmetric oxidation is possible. This study describes a reverse-phase high-performance liquid chromatographic (HPLC) method for the quantitation of PNO and a chiral-phase HPLC method for the determination of the enantiomeric ratio of PNO. In vitro microsomal N-oxidation of pargyline was found to be highly stereoselective in a number of species, with the (+)-enantiomer being formed preferentially. This metabolic transformation was stereospecific when purified porcine hepatic FMO was used as the enzyme source.
Hadley
M R
MR
Department of Pharmacy, King's College London, England.
Svajdlenka
E
E
Damani
L A
LA
Oldham
H G
HG
Tribe
J
J
Camilleri
P
P
Hutt
A J
AJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000201:enzymology; D009904:Optical Rotation; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism; D010293:Pargyline / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013552:Swine
C028576:pargyline N-oxide; D010293:Pargyline; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)