Ian M Coupar, Helen R Irving, David T Manallack, Yean Y Tan, Fadi Ayad, Juliana Di Iulio, Nathalie Tochon-Danguy, Magdy N Iskander
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Parkville, Vic., Australia.
The Journal of pharmacy and pharmacology 2012 AugThe 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. Three compounds were tested for affinity at the 5-HT(4) 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. The three compounds all had agonist properties at the 5-HT(4) receptor but their efficacy differed in the different functional tests. Compound 3 had the highest affinity for the 5-HT(4) 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. Of the compounds tested, compound 3 was the most promising 5-HT(4) receptor agonist and the results highlight the value of using human tissue in functional tests when assessing compounds for potential activity. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Ian M Coupar, Helen R Irving, David T Manallack, Yean Y Tan, Fadi Ayad, Juliana Di Iulio, Nathalie Tochon-Danguy, Magdy N Iskander. Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors. The Journal of pharmacy and pharmacology. 2012 Aug;64(8):1099-106
PMID: 22775213
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