Correlation of chick embryo teratogenicity with the nicotinic activity of a series of tetrahydropyrimidines

Abstract

Nicotine, anabasine, nornicotine, p-nicotyrine, and 34 substituted 1,4,5,6-tetrahydropyrimidines, 2-imidazolines, and 4,5,6,7-tetrahydro-l, H-1, 3-diazepines were injected into the yolk sac of chick eggs on day 4 of incubation at a dose of 1 or 2.5 mglegg. The embryopathic results were compared with toxicological and pharmacological data and chemical structure. Abnormalities were similar to those induced by nicotine and anabasine but only compounds with nicotinic activity, as measured on the chick spinalis muscle, were teratogenic. All but one of the teratogenic compounds were 2-pyridylsubstituted, and in this series teratogenic and nicotinic potency decreased in the order 3'->4'-> 2'-pyridyl.. There was a highly significant negative correlation between spine length and nicotinic potency of the compounds.

Investigation of the Possible Pharmacologically Active Forms of the Nicotinic Acetylcholine Receptor Agonist Anabaseine

“…The ability of a variety of 2-(aryl)-1,4,5,6-tetrahydropyrmidines to block neuromuscular nAChRs and produce teratogenic effects in chick embryos was reported long ago [45,46]. Some of these compounds were reported to be nAChR agonists.…”

Solanaceae Juss.

“…Anabasine appears to be about half as toxic as nicotine in producing acute nicotinic effects but is much less potent as a central nervous system stimulant (Upshall 1972;Sloan et al 1988). It is present as R and S enantiomers, the R -anabasine being somewhat more potent (Lee et al 2006).…”

“…It is present as R and S enantiomers, the R -anabasine being somewhat more potent (Lee et al 2006). Both are potent teratogens in the chick embryo model (Landauer 1960;Upshall 1972). Both are potent teratogens in the chick embryo model (Landauer 1960;Upshall 1972).…”

Separation and measurement of plant alkaloid enantiomers by RP‐HPLC analysis of their Fmoc‐Alanine analogs

“…Anabasine (2) is present in N. glauca as a racaemic mixture , Lee et al, 2006, and coniine (3) is a racaemic mixture in C. maculatum (Marion, 1950). Nornicotine (4), an enantiomeric alkaloid found in N. tabacum, has been shown to induce malformations in chick embryos (Upshall, 1972).…”