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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #300548

Title: Plant alkaloids that cause developmental defects through the disruption of cholinergic neurotransmission

Author
item Green, Benedict - Ben
item Lee, Stephen
item Welch, Kevin
item Panter, Kip

Submitted to: Birth Defects Research Part C: Embryo Today: Reviews
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2013
Publication Date: 12/16/2013
Publication URL: https://handle.nal.usda.gov/10113/5418164
Citation: Green, B.T., Lee, S.T., Welch, K.D., Panter, K.E. 2013. Plant alkaloids that cause developmental defects through the disruption of cholinergic neurotransmission. Birth Defects Research Part C: Embryo Today: Reviews. 99:235-246.

Interpretive Summary: The exposure of a developing embryo to alkaloids from plants can cause birth defects in humans and animals. These defects may have multiple causes but those induced by piperidine and quinolizidine alkaloids arise from the inhibition of fetal movement. Structure-function studies have shown that plant alkaloids with a piperidine ring and a minimum of a three-carbon side-chain alpha to the piperidine nitrogen are teratogenic. Further studies determined that an unsaturation in the piperidine ring as occurs in gamma coniceine, or anabaseine enhances the toxic and teratogenic activity while the N-methyl derivatives are less potent. In this article we review the molecular mechanism of alkaloid action and alkaloid biological activities. These alkaloids, a group of piperidine and quinolizidine alkaloid teratogens that impart a series of flexure type skeletal defects and cleft palate in animals.

Technical Abstract: The exposure of a developing embryo or fetus to alkaloids from plants, plant products, or plant extracts has the potential to cause developmental defects in humans and animals. These defects may have multiple causes but those induced by piperidine and quinolizidine alkaloids arise from the inhibition of fetal movement and are generally referred to as multiple congenital contracture-type deformities. These skeletal deformities include arthrogyrposis, kyposis, lordosis, scoliosis, and torticollis, associated secondary defects and cleft palate. Structure-function studies have shown that plant alkaloids with a piperidine ring and a minimum of a three-carbon side-chain alpha to the piperidine nitrogen are teratogenic. Further studies determined that an unsaturation in the piperidine ring as occurs in gamma coniceine, or anabaseine enhances the toxic and teratogenic activity while the N-methyl derivatives are less potent. Enantiomers of the piperidine teratogens, coniine, ammodendrine and anabasine also exhibit differences in biological activity as shown in cell culture studies suggesting variability in the activity due to the optical rotation at the chiral center of these stereoisomers. In this article we review the molecular mechanism at the nicotinic pharmacophore and biological activities, as it is currently understood, of a group of piperidine and quinolizidine alkaloid teratogens that impart a series of flexure type skeletal defects and cleft palate in animals.