In vitro microsomal [correction of mircosomal] metabolism of N-benzyl and N-benzoylnornicotine derivates by rat.
The in vitro hepatic microsomal metabolism of N-1'-benzylnornicotine, N-l'-(p-chlorobenzyl)nornicotine, N-1'-benzoylnornicotine and N-1'-(p-chlorobenzoyl) nornicotine was studied using hepatic washed rat microsomal preparations fortified with NADPH. Substrates and their potential metabolites were synthesized, characterised by spectral methods, and separated using a reverse phase HPLC system consisted of a C18 column and a mobile phase composition of acetonitrile: phosphate buffer. Substrates and their potential metabolites were extracted from biological systems with dichloromethane. Metabolites detected were compared with retention times and uv spectra of authentic standards. Metabolic experiments indicated that oxidative dealkylation leading to the formation of nornicotine and the corresponding aldehydes was a major route of metabolism for N-alkylnornicotine substrates. In addition, N-1'-(p-chlorobenzyl)nornicotine produced the corresponding lactam and amide metabolites. N-Acylnornicotines were hydrolysed to nornicotine.
Yilmaz
F
F
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Haydarpaşa, Instabul, Turkey.
Kartal
F Aricioglu
FA
Ulgen
M
M
Gorrod
John W
JW
D000818:Animals; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D009538:Nicotine; C005311:nornicotine
Anal Chem. 1988 Oct 1;60(19):2120-7
3239791
Eur J Drug Metab Pharmacokinet. 2000 Apr-Jun;25(2):145-50
11112096
Biochem Pharmacol. 1990 Jan 1;39(1):R1-4
2297350
Adv Exp Med Biol. 1991;283:657-64
1906229
Farmaco. 1999 May 30;54(5):331-7
10418125
Planta. 2000 Feb;210(3):510-4
10750910
Methods Enzymol. 1978;52:83-9
672658
J Med Chem. 1976 Sep;19(9):1168-9
978682
Drug Metab Rev. 1991;23(1-2):3-41
1868776