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 2was 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 language | English |
|---|---|
| Pages (from-to) | 1099-1106 |
| Number of pages | 8 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 64 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2012 |
| Externally published | Yes |