Barker David, Lin Diana H-S, Carland Jane E, Chu Cindy P-Y, Chebib Mary, Brimble Margaret A, Savage G Paul, McLeod Malcolm D
School of Chemistry, F11, University of Sydney, Camperdown, NSW 2006, Australia.
Bioorg Med Chem. 2005 Jul 15;13(14):4565-75. doi: 10.1016/j.bmc.2005.04.054.
Bicyclic analogues of methyllycaconitine (MLA), such as 12, have been synthesised that incorporate the C1-OMe substituent present in the natural product. Electrophysiology experiments using Xenopus oocytes expressing nicotinic acetylcholine receptors (nAChRs) were conducted on these analogues and a related tricyclic analogue 2. The most potent compound, 2, was an antagonist at all receptors studied but displayed different antagonist effects at each receptor subtype. This study more clearly defines the biological effects of MLA analogues at nAChRs and demonstrates that these analogues are not selective ligands for the alpha7 nAChR subtype.
已合成了甲基lycaconitine（MLA）的双环类似物，如12，其包含天然产物中存在的C1 - OMe取代基。对这些类似物以及相关的三环类似物2进行了使用表达烟碱型乙酰胆碱受体（nAChRs）的非洲爪蟾卵母细胞的电生理学实验。最有效的化合物2是所研究的所有受体的拮抗剂，但在每种受体亚型上表现出不同的拮抗作用。这项研究更清楚地定义了MLA类似物在nAChRs上的生物学效应，并证明这些类似物不是α7 nAChR亚型的选择性配体。
