The interaction of antidepressant drugs with enteric 5-HT7 receptors.
Article Details
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Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M
The interaction of antidepressant drugs with enteric 5-HT7 receptors.
Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9.
- PubMed ID
- 10997731 [ View in PubMed]
- Abstract
In this study the functional interaction of the antidepressant drugs amitriptyline, mianserin, maprotiline, imipramine, fluoxetine and the putative antidepressant drug flibanserin has been studied on 5-HT7-mediated responses to 5-carboxamidotryptamine (5-CT) in the guinea-pig ileum. 5-CT induced a concentration-dependent inhibition of the contractile response to substance P (100 nM). Except for fluoxetine and flibanserin, all the antidepressants antagonized by different degrees the 5-CT inhibitory response with the following rank affinity order: mianserin > maprotiline > imipramine > amitriptyline. Mianserin was the only antidepressant to show a profile of competitive antagonism at 5-HT7 receptors in a tenfold range of concentrations (0.1-1 microM), with an affinity (pA2) value of 8.1 +/- 0.6. The antagonism of the other antidepressants was not concentration-dependent (amitriptyline) or was associated with slight or moderate reduction of the maximal 5-CT response (imipramine or maprotiline). The apparent affinity (pKB) values were: amitriptyline, 7.0 +/- 0.2; maprotiline, 7.3 +/- 0.6; imipramine, 7.2 +/- 0.4. Our results show that various antidepressant drugs belonging to different chemical classes behave as antagonists at enteric 5-HT7 receptors through competitive or allosteric mechanisms. This evidence extends our previous findings demonstrating the interaction of antidepressants with other 5-HT receptors, namely 5-HT3 and 5-HT4 receptors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amitriptyline 5-hydroxytryptamine receptor 7 Protein Humans UnknownAntagonistDetails Imipramine 5-hydroxytryptamine receptor 7 Protein Humans UnknownAntagonistDetails Maprotiline 5-hydroxytryptamine receptor 7 Protein Humans UnknownAntagonistDetails Mianserin 5-hydroxytryptamine receptor 7 Protein Humans UnknownAntagonistDetails