Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine.
This paper reports the results of studies on the in vivo metabolic fate of the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine) in New Zealand white rabbits. Two previously characterized metabolites, 5-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (5-hydroxycotinine) and 2-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one, were present in low concentrations in the urine of the treated animals. The major urinary metabolite of beta-nicotyrine was identified as cis-3'-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (cis-3'-hydroxycotinine), the diastereoisomer of the major urinary metabolite of (S)-nicotine. The pathway leading to cis-3'-hydroxycotinine is proposed to proceed via autoxidation of 2-hydroxy-1-methyl-5-(3-pyridinyl)pyrrole, a postulated cytochrome P450-generated metabolite of beta-nicotyrine, followed by reduction of the carbon-carbon double bond present in the resulting 3-hydroxy-3-pyrrolin-2-one species. This proposal is supported by the in vivo biotransformation of 2-acetoxy-1-methyl-5-(3-pyridinyl)pyrrole, a latent form of the putative hydroxypyrrole intermediate, to cis-3'-hydroxycotinine. The in vivo conversion of 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one to 5-hydroxycotinine is offered as evidence that supports the proposed reduction step.
Liu
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X
Harvey W. Peters Center, Department of Chemistry, and Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia 24061, USA.
Castagnoli
K
K
Van Der Schyf
C J
CJ
Castagnoli
N
N
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D008658:Inactivation, Metabolic; D007306:Insecticides / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010944:Plants; D011725:Pyridines / Q000493:pharmacokinetics*; D011817:Rabbits
D007306:Insecticides; D011725:Pyridines; C008615:alpha-nicotyrine