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

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Lochner, Martin 
Thompson, Andrew J 


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-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). 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.



5-HT(3), Amygdala, Antagonist, Anxiety, Binding site, Cognition, Cys-loop, Depression, Hippocampus, Ligand docking, Memory, Muscarinic, Scopolamine, Animals, Atropine, Binding, Competitive, Dose-Response Relationship, Drug, Female, Guinea Pigs, HEK293 Cells, Humans, Male, Muscarinic Antagonists, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Serotonin, 5-HT3, Scopolamine, Serotonin 5-HT3 Receptor Antagonists, Xenopus laevis

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Elsevier BV
British Heart Foundation (None)
Our thanks are given to John Peters (University of Dundee) for the 5-HT3A subunit. ML thanks the Swiss National Science Foundation for financial support (SNSF- professorship PP00P2_123536 and PP00P2_146321). AJT thanks the British Heart Foundation for financial support (PG/13/39/30293).