دورية أكاديمية
The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.
| العنوان: | The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors. |
|---|---|
| المؤلفون: | Lochner, Martin, Thompson, Andrew J |
| بيانات النشر: | Elsevier BV //dx.doi.org/10.1016/j.neuropharm.2016.04.027 Neuropharmacology |
| سنة النشر: | 2016 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | 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, Tertiary, Receptors, Serotonin |
| الوصف: | 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. ; 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). ; This is final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neuropharm.2016.04.027Test |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/255834Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/255834Test |
| حقوق: | Attribution-NonCommercial-NoDerivs 2.0 UK: England & Wales ; http://creativecommons.org/licenses/by-nc-nd/2.0/ukTest/ |
| رقم الانضمام: | edsbas.CD08D3EC |
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