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

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

  • Lochner M Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern, CH-3012, Switzerland. Electronic address: martin.lochner@dcb.unibe.ch.
  • Thompson AJ Department of Pharmacology, Tennis Court Road, Cambridge, CB2 1PD, UK. Electronic address: ajt44@cam.ac.uk.
  • 2016-04-26
Published in:
  • Neuropharmacology. - 2016
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
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/173311
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