The interaction of antidepressant drugs with enteric 5-HT7 receptors

Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. doi: 10.1007/s002100000295.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Guinea Pigs
  • Ileum / drug effects
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Receptors, Serotonin / drug effects*
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Antidepressive Agents
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • serotonin 7 receptor
  • Serotonin
  • 5-carboxamidotryptamine