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United States Department of Agriculture

Agricultural Research Service

Research Project: THE TOXICITY OF PYRROLIZIDINE ALKALOID-CONTAINING PLANTS AND OTHER HEPATOTOXIC AND NEUROTOXIC PLANTS Title: Steroselective Potencies and Relative Toxicities of Coniine Enantiomers

Authors
item Lee, Stephen
item Green, Benedict
item Welch, Kevin
item Pfister, James
item Panter, Kip

Submitted to: Chemical Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 1, 2008
Publication Date: September 3, 2008
Citation: Lee, S.T., Green, B.T., Welch, K.D., Pfister, J.A., Panter, K.E. 2008. Steroselective Potencies and Relative Toxicities of Coniine Enantiomers. Chemical Research in Toxicology. 21(10): 2061-2064. DOI 10.1021/tx800229w

Interpretive Summary: Coniine, one of the major toxic chemicals present in poison hemlock., occurs in two forms. In this study, we separated the two forms of coniine and determined the biological activity of each form. The relative potencies of these forms on cells had the rank order of (-)-coniine > (')-coniine > (+)-coniine. A mouse bioassay was used to determine the relative lethalities of the coniine forms. The rank order of toxicity of the coniine forms was (-)-coniine > (')-coniine > (+)-coniine. The results from this study demonstrate that there is a difference in the potencies of the forms of coniine in cells that directly correlates with the relative toxicities of the forms in mice.

Technical Abstract: Coniine, one of the major toxic alkaloids present in poison hemlock (Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and determined the biological activity of each enantiomer in vitro and in vivo. The relative potencies of these enantiomers on TE-671 cells expressing human fetal nicotinic neuromuscular receptors had the rank order of (-)-coniine > (')-coniine > (+)-coniine. A mouse bioassay was used to determine the relative lethalities of (-)-, (')- and (+)-coniine in vivo. The LD50s of the coniine enantiomers were 7.0, 7.7, and 12.1 mg/kg for the (-)-, (')-, and (+)- forms of coniine, respectively. The results from this study demonstrate that there is a stereoselective difference in the in vitro potencies of the enantiomers of coniine that directly correlates with the relative toxicities of the enantiomers in vivo.

Last Modified: 10/21/2014