PSAB-OFP, a selective α7 nicotinic receptor agonist, is also a potent agonist of the 5-HT3 receptor

被引：35

作者：

Broad, LM ^{[1
]}

Felthouse, C ^{[1
]}

Zwart, R ^{[1
]}

McPhie, GI ^{[1
]}

Pearson, KH ^{[1
]}

Craig, PJ ^{[1
]}

Wallace, L ^{[1
]}

Broadmore, RJ ^{[1
]}

Boot, JR ^{[1
]}

Keenan, M ^{[1
]}

Baker, SR ^{[1
]}

Sher, E ^{[1
]}

机构：

[1] Eli Lilly & Co Ltd, Lilly Res Ctr Ltd, Windlesham GU20 6PH, Surrey, England

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2002年 / 452卷 / 02期

关键词：

alpha a7 nicotinic receptor; 5-HT3; receptor; cross-reactivity; spiroazabicyclic;

D O I：

10.1016/S0014-2999(02)02273-2

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

5-Hydroxytryptamine 3 (5-HT3) and alpha7 nicotinic receptors share high sequence homology and pharmacological cross-reactivity. An assessment of the potential role of alpha7 receptors in many neurophysiological processes, and hence their therapeutic value, requires the development of selective alpha7 receptor agonists. We used a recently reported selective alpha7 receptor agonist, (R)-(-)-5'Phenylspiro[1-azabicyclo[2.2.2] octane-3,2'-(3H)furo[2,3-b]pyridine (PSAB-OFP) and confirmed its activity on human recombinant alpha7 receptors. However, PSAB-OFP also displayed high affinity binding to 5-HT3 receptors. To assess the functional activity of PSAB-OFP on 5-HT3 receptors we studied recombinant human 5-HT3 receptors expressed in Xenopus oocytes, as well as native mouse 5-HT3 receptors expressed in N1E-115 neuroblastoma cells, using whole-cell patch clamp and Ca2+ imaging. Our results show that PSAB-OFP is an equipotent, partial agonist of both alpha7 and 5-HT3 receptors. We conclude that it will be necessary to identify the determinant of this overlapping pharmacology in order to develop more selective alpha7 receptor ligands. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

页码：137 / 144

页数：8

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