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United States Department of Agriculture

Agricultural Research Service

Research Project: Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems

Location: Poisonous Plant Research

Title: Stereoselective potencies and relative toxicities of y-Coniceine and N-Methylconiine enantiomers

Authors
item Lee, Stephen
item Green, Benedict
item Welch, Kevin
item Jordan, Glenn -
item Zhang, Qian -
item Panter, Kip
item Hughes, David -
item Cheng-Wei, Tom -
item Pfister, James
item Gardner, Dale

Submitted to: Chemical Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 1, 2013
Publication Date: March 20, 2013
Citation: Lee, S.T., Green, B.T., Welch, K.D., Jordan, G.T., Zhang, Q., Panter, K.E., Hughes, D., Cheng-Wei, T.C., Pfister, J.A., Gardner, D.R. 2013. Stereoselective potencies and relative toxicities of y-Coniceine and N-Methylconiine enantiomers. Chemical Research in Toxicology. 23:616-21.

Interpretive Summary: '-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum). In this study, we prepared '-coniceine and the enantiomers (mirror images) of N-methylconiine and determined the biological activity of '-coniceine and each of the N-methylconiine enantiomers in vitro and in vivo. The relative potencies of these piperidine alkaloids on cells expressing human fetal muscle-type nicotinic acetylcholine receptors had the rank order of '-coniceine > (-)-N-methylconiine > (')-N-methylconiine > (+)-N-methylconiine. The relative lethalities of '-coniceine, (-)-, (')- and (+)-N-methylconiine in vivo using a mouse bioassay were 4.4, 16.1, 17.8, and 19.2 mg/kg, respectively. The results from this study suggest '-coniceine is a more potent toxin than the enantiomers of N-methylconiine and that there is a stereoselective difference in the in vitro potencies of the enantiomers of N-methylconiine that correlates with the relative toxicities of the enantiomers in vivo.

Technical Abstract: '-Coniceine, coniine, and N-methylconiine are toxic alkaloids present in poison hemlock (Conium maculatum). We previously reported the comparison of the relative potencies of (+)- and (-)-coniine enantiomers. In this study, we synthesized '-coniceine and the enantiomers of N-methylconiine and determined the biological activity of '-coniceine and each of the N-methylconiine enantiomers in vitro and in vivo. The relative potencies of these piperidine alkaloids on cells expressing human fetal muscle-type nicotinic acetylcholine receptors had the rank order of '-coniceine > (-)-N-methylconiine > (')-N-methylconiine > (+)-N-methylconiine. The relative lethalities of '-coniceine, (-)-, (')- and (+)-N-methylconiine in vivo using a mouse bioassay were 4.4, 16.1, 17.8, and 19.2 mg/kg, respectively. The results from this study suggest '-coniceine is a more potent agonist than the enantiomers of N-methylconiine and that there is a stereoselective difference in the in vitro potencies of the enantiomers of N-methylconiine that correlates with the relative toxicities of the enantiomers in vivo.

Last Modified: 4/20/2014