Methyllycaconitine analogues have mixed antagonist effects at nicotinic acetylcholine receptors

被引：61

作者：

Barker, D

Lin, DHS

Carland, JE

Chu, CPY

Chebib, M

Brimble, MA

Savage, GP

McLeod, MD

机构：

[1] Univ Sydney, Sch Chem, Camperdown, NSW 2006, Australia

[2] Univ Sydney, Fac Pharm, Camperdown, NSW 2006, Australia

[3] Univ Auckland, Dept Chem, Auckland 1, New Zealand

[4] CSIRO Mol Sci, Clayton, Vic 3169, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 14期

关键词：

D O I：

10.1016/j.bmc.2005.04.054

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha 7 nAChR subtype. (c) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：4565 / 4575

页数：11

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