Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors

Ian Michael Coupar, Helen Ruth Irving, David Thomas Manallack, Yean Yeow Tan, Fadi Ayad, Juliana L Di Iulio, Nathalie Tochon-Danguy, Magdy Naguib Iskander

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives The aim was to examine the biological activity of 5-methoxytryptamine derivatives at the 5-hydroxytryptamine (5-HT)4 receptor to explore the effect of substitution on the aliphatic amine of the 5-methoxyamine scaffold. Methods Three compounds were tested for affinity at the 5-HT4 receptor by radioligand binding and functional activity using guinea-pig ileum and human colon circular muscle preparations and also in the mouse whole gut transit test. Key findings The three compounds all had agonist properties at the 5-HT4 receptor but their efficacy differed in the different functional tests. Compound 3 had the highest affinity for the 5-HT4 receptor and was a full agonist at relaxing human colon circular muscle with efficacy closest to 5-HT. Compounds 1 and 2 were partial agonists in this assay with lower efficacies; compound 2 was a full agonist in the guinea-pig ileum assay whereas compound 3 was a partial agonist. Compounds 1 and 2 also showed activity in the mouse gut transit assay while compound 3 had no activity. Conclusions Of the compounds tested, compound 3 was the most promising 5-HT4 receptor agonist and the results highlight the value of using human tissue in functional tests when assessing compounds for potential activity.
Original languageEnglish
Pages (from-to)1099 - 1106
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume64
Issue number8
DOIs
Publication statusPublished - 2012

Cite this

Coupar, Ian Michael ; Irving, Helen Ruth ; Manallack, David Thomas ; Tan, Yean Yeow ; Ayad, Fadi ; Di Iulio, Juliana L ; Tochon-Danguy, Nathalie ; Iskander, Magdy Naguib. / Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors. In: Journal of Pharmacy and Pharmacology. 2012 ; Vol. 64, No. 8. pp. 1099 - 1106.
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abstract = "Objectives The aim was to examine the biological activity of 5-methoxytryptamine derivatives at the 5-hydroxytryptamine (5-HT)4 receptor to explore the effect of substitution on the aliphatic amine of the 5-methoxyamine scaffold. Methods Three compounds were tested for affinity at the 5-HT4 receptor by radioligand binding and functional activity using guinea-pig ileum and human colon circular muscle preparations and also in the mouse whole gut transit test. Key findings The three compounds all had agonist properties at the 5-HT4 receptor but their efficacy differed in the different functional tests. Compound 3 had the highest affinity for the 5-HT4 receptor and was a full agonist at relaxing human colon circular muscle with efficacy closest to 5-HT. Compounds 1 and 2 were partial agonists in this assay with lower efficacies; compound 2 was a full agonist in the guinea-pig ileum assay whereas compound 3 was a partial agonist. Compounds 1 and 2 also showed activity in the mouse gut transit assay while compound 3 had no activity. Conclusions Of the compounds tested, compound 3 was the most promising 5-HT4 receptor agonist and the results highlight the value of using human tissue in functional tests when assessing compounds for potential activity.",
author = "Coupar, {Ian Michael} and Irving, {Helen Ruth} and Manallack, {David Thomas} and Tan, {Yean Yeow} and Fadi Ayad and {Di Iulio}, {Juliana L} and Nathalie Tochon-Danguy and Iskander, {Magdy Naguib}",
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Coupar, IM, Irving, HR, Manallack, DT, Tan, YY, Ayad, F, Di Iulio, JL, Tochon-Danguy, N & Iskander, MN 2012, 'Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors', Journal of Pharmacy and Pharmacology, vol. 64, no. 8, pp. 1099 - 1106. https://doi.org/10.1111/j.2042-7158.2012.01500.x

Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors. / Coupar, Ian Michael; Irving, Helen Ruth; Manallack, David Thomas; Tan, Yean Yeow; Ayad, Fadi; Di Iulio, Juliana L; Tochon-Danguy, Nathalie; Iskander, Magdy Naguib.

In: Journal of Pharmacy and Pharmacology, Vol. 64, No. 8, 2012, p. 1099 - 1106.

Research output: Contribution to journalArticleResearchpeer-review

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