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

Lochner, Martin; Thompson, Andrew James (2016). The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors. Neuropharmacology, 108, pp. 220-228. Elsevier 10.1016/j.neuropharm.2016.04.027

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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 [3H]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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Lochner, Martin and Thompson, Andrew James

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
600 Technology > 610 Medicine & health

ISSN:

0028-3908

Publisher:

Elsevier

Funders:

[42] Schweizerischer Nationalfonds
[UNSPECIFIED] British Heart Foundation

Language:

English

Submitter:

Martin Lochner

Date Deposited:

15 Jun 2016 11:46

Last Modified:

15 Jun 2016 11:46

Publisher DOI:

10.1016/j.neuropharm.2016.04.027

PubMed ID:

27108935

BORIS DOI:

10.7892/boris.82240

URI:

https://boris.unibe.ch/id/eprint/82240

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