N-Methylnornicotinium ion has been identified as a metabolite in the urine of male Hartley guinea pigs that had been chronically dosed ip with R-(+)-nicotine. Under similar conditions, S-(-)-nicotine is not biotransformed into this metabolite. The metabolite was isolated and purified by preparative high performance cation-exchange liquid chromatography. The structural identity of the metabolite was determined by UV spectrophotometric analysis and sodium borohydride reduction followed by GLC-mass spectrometric analysis, and Fourier transform 1H NMR spectrometric analysis. The formation of this metabolic product from nicotine represents a unique example of N-demethylation and N-methylation reactions both occurring within the same molecule.
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Enantioselective metabolism during continuous administration of S-(-)- and R-(+)-nicotine isomers to guinea-pigs.
J Pharm Pharmacol
December 1988
College of Pharmacy, Division of Medicinal Chemistry and Pharmacognosy, University of Kentucky, Lexington 40536-0083.
The S-(-)- and R-(+)-nicotine isomers were administered subcutaneously via Alzet osmotic pumps to male Hartley guinea-pigs (n = 5 with each isomer) over a 23-day period. Estimated dosage rate throughout the experiment was 0.6 mg-1.
View Article and Find Full Text PDFBiotransformation 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.
J Pharm Pharmacol
November 1988
Division of Medicinal Chemistry, University of Kentucky, Lexington 40536-0053.
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.
View Article and Find Full Text PDFThe in vivo biotransformation and tissue distribution of the methylated nicotine metabolite R-(+)-[14C-NCH3]N-methylnicotinium acetate was studied in the guinea pig. The detection and quantification of 24-hr urinary metabolites after ip injection was determined by cation-exchange HPLC interfaced to a radiochemical flowthrough detector. The urinary metabolite profile consisted of five peaks.
View Article and Find Full Text PDFN-Methylnornicotinium ion, a new in vivo metabolite of R-(+)-nicotine.
Drug Metab Dispos
September 1985
N-Methylnornicotinium ion has been identified as a metabolite in the urine of male Hartley guinea pigs that had been chronically dosed ip with R-(+)-nicotine. Under similar conditions, S-(-)-nicotine is not biotransformed into this metabolite. The metabolite was isolated and purified by preparative high performance cation-exchange liquid chromatography.
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