A novel pyridine derivative, 3,5-bis-(1-methyl-pyrrolidin-2-yl)-pyridine, and a pair of diastereomers of 1,1′-dimethyl-[2,3′]bipyrrolidinyl were isolated from the root of Nicotiana tabacum plants and identified as novel alkaloids by GC-MS analysis. The structures of these new alkaloids were confirmed by total synthesis. The affinities of these novel alkaloids, and other structurally related compounds for α4β2*, α7* neuronal nicotinic acetylcholine receptors (nAChRs), and for nAChRs mediating nicotine-evoked dopamine release from rat striatum were also assessed. The results indicate that these compounds do not interact with α7* nAChRs, but inhibit [3H]nicotine binding to the α4β 2* nAChR subtype. The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum.
|Number of pages||11|
|State||Published - Dec 22 2005|
Bibliographical noteFunding Information:
This project was funded under the NIH grant number U19 DA 017548.
- Neuronal nicotinic acetylcholine receptors
- Nicotiana tabacum
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Pharmacology, Toxicology and Pharmaceutics (all)