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KMID : 0614019890050010031
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Journal of Pharmaceutical Sciences (C.N.U.)
1989 Volume.5 No. 1 p.31 ~ p.36
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Liver and Lung Microsomal Metabolism of the Tobacco Alkaloid β-Nicotyrine
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Shigenaga M.K.
Kim B. H.
Caldera-Munoz P.
Cairns T.
Jacob III P.
Castagnoli N.
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Abstract
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The in vitro metabolic fate of β-nicotyrine has been examined in rabbit lung and liver microsomal preparations as part of an effort to characterize the formation of potentially reactive metabolic species that may contribute to the toxic properties of tobacco products. HPLC analysis revealed the formation of an unstable metabolite which displayed HPLC-MS/MS characteristics consistent with the structure 1-methyl-5-(3-pyridyl)-3-pyrrolin-2-one. Attempted synthesis of this pyrrolinone, however, resulted in the isolation of the isomeric 1-methyl-5-(3-pyridyl)-2-pyrrolin-2-one. The HPLC, diode array UV, and mass spectral characteristics of this Δ^4,5-isomer proved to be identical with those of the metabolite derived from β-nicotyrine. Studies in D_2O suggest that the 2- and 3-pyrrolinones are in equilibrium in aqueous solution. The metabolite undergoes autoxidation, possible via radical intermediates, to yield 1-methyl-5-(3-pyridyl)-5-hydroxy-3-pyrrolin-2-one.
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