The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors

NEUROPHARMACOLOGY

卷:108

Article

Lochner, Martin¹  Thompson, Andrew J.² 

[1] Univ Bern, Dept Chem & Biochem, Freiestr 3, CH-3012 Bern, Switzerland

[2] Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England

关键词: 5-HT3;    Cys-loop;    Binding site;    Ligand docking;    Scopolamine;    Muscarinic;    Antagonist;    Muscarinic;    Anxiety;    Cognition;    Memory;    Depression;    Hippocampus;    Amygdala;   

DOI  :  10.1016/j.neuropharm.2016.04.027

来源: Elsevier

【 摘 要 】

Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT(3)A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 mu M. Competitive antagonism was shown by Schild plot (pA(2) = 5.02) and by competition with the 5-HT3 receptor antagonists [H-3]granisetron (K-i = 6.76 mu M) and G-FL (K-i = 4.90 mu M). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 mu M, and competed with G-FL with a K-i of 7.94 mu M. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (K-i = 6.5 mu M). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licensesiby/4.0/).

【 授权许可】

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