Wei Xiaochen, Sumithran Sangeetha P, Deaciuc A Gabriela, Burton Harold R, Bush Lowell P, Dwoskin Linda P, Crooks Peter A
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Life Sci. 2005 Dec 22;78(5):495-505. doi: 10.1016/j.lfs.2005.09.009. Epub 2005 Sep 28.
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 alpha4beta2*, alpha7* 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 alpha7* nAChRs, but inhibit [3H]nicotine binding to the alpha4beta2* nAChR subtype. The results also demonstrate that these compounds act as antagonists at nAChRs mediating nicotine-evoked dopamine release from rat striatum.
从烟草植物的根部分离出一种新型吡啶衍生物3,5-双-(1-甲基-吡咯烷-2-基)-吡啶以及一对1,1'-二甲基-[2,3']联吡咯烷基的非对映异构体，并通过气相色谱-质谱分析将其鉴定为新型生物碱。这些新生物碱的结构通过全合成得到确证。还评估了这些新型生物碱以及其他结构相关化合物对α4β2*、α7神经元烟碱型乙酰胆碱受体（nAChRs），以及对介导尼古丁诱发大鼠纹状体多巴胺释放的nAChRs的亲和力。结果表明，这些化合物不与α7 nAChRs相互作用，但抑制[3H]尼古丁与α4β2* nAChR亚型的结合。结果还表明，这些化合物在介导尼古丁诱发大鼠纹状体多巴胺释放的nAChRs上起拮抗剂作用。
