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

ABSTRACT: 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 ?M. 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 ?M) and G-FL (Ki = 4.90 ?M). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 ?M, and competed with G-FL with a Ki of 7.94 ?M. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 ?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.

SUBMITTER: Lochner M

PROVIDER: S-EPMC4920643 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Lochner Martin M Thompson Andrew J AJ

Neuropharmacology 20160422

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 rever ...[more]

PMID: 27108935

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Project description:PURPOSE: To investigate the effect of atropine on the development of spectacle lens induced myopia in the mouse and to determine if the level of mRNAs for the muscarinic receptor subtypes (M(1) - M(5)) is affected by atropine treatment. METHODS: Experimental myopia was developed in Balb/CJ (BJ) mice by placing -10 diopter spectacle lens on post-natal day 10 over the right eyes of 150 mice (n=10 in each group, 5 repetitions) for six weeks. After 2 weeks of lens wearing, the atropine group received a daily sub-conjunctival injection (10 µl) of 1% atropine sulfate and the saline group received daily 10 µl of 0.9% normal saline for 4 weeks. In addition, myopia was developed in C57BL/6 (B6) mice by placing -10 D spectacle lens on post-natal day 10 over the right eyes of 60 mice (n=10 in each group, 2 repetitions) for six weeks with and without atropine treatment. Refraction and axial length was measured at 2, 4, and 6 weeks after treatments. RT-PCR and northern blots were performed using specific primers for M(1)-M(5), and products sequenced. Real-time PCR was used to quantify message levels. RESULTS: Axial length of myopic eyes was 111% of their controls without atropine treatment and 103% of controls after atropine (p<0.01). Refraction shifted from myopic to emmetropic after atropine was administered in both pigmented and non-pigmented eyes. Corneal thickness, anterior chamber depth, corneal curvature and retinal thickness were not significantly different with and without atropine treatment (p=0.14). The lens thickness and vitreous chamber depth were significantly reduced after receiving atropine (p<0.05). Real-time PCR showed that message levels for M(1), M(3), and M(4) were upregulated in myopic sclera after atropine treatment, but M(2) and M(5) showed little change. CONCLUSIONS: The present study shows that 1% atropine reduces myopia progression in both pigmented and non-pigmented mice eyes. Axial length and vitreous chamber depth appear to be the main morphological parameters related to myopia. The results suggest that atropine may act on one or more muscarinic receptors to differentially regulate expression levels of specific receptors.

Dataset Information

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

Publications

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

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