Biotransformation of primary nicotine metabolites: metabolism of R-(+)-[3H-N'-CH3; 14C-N-CH3] N-methylnicotinium acetate--the use of double isotope studies to determine the in-vivo stability of the N-methyl groups of N-methylnicotinium ion.
The in-vivo metabolism of R-(+)-[3H-N'-CH3; 14C-N-CH3]-N-methylnicotinium acetate (NMN) was studied in the guinea-pig to determine the in-vivo stability of the N-methyl and N'-methyl groups of this primary nicotine metabolite. The results showed that N-demethylation does not occur. However, losses of 34 and 36%, respectively, of the 3H label in the N'-CH3 group of urinary NMN and the secondary metabolite, N-methyl-N'-oxonicotinium ion (NMNO), were observed. These results suggest that biotransformation of NMN may involve either an initial N'-demethylation step to N-methylnornicotinium ion (NMNor) followed by N'-methylation back to NMN, or the formation of an N'-methylene iminium species, which may be reductively converted back to NMN.
Pool
W F
WF
Division of Medicinal Chemistry, University of Kentucky, Lexington 40536-0053.
Crooks
P A
PA
D000818:Animals; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D004822:Epididymis / Q000378:metabolism; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000652:urine; D011726:Pyridinium Compounds
D011726:Pyridinium Compounds; C047661:N-methylnicotinium; D009538:Nicotine