STW 5 in a model of 5-HT3 receptor mediated ileal contraction in vitro

Introduction: 5-HT3 receptors are widely distributed in the gastrointestinal tract and are significantly involved in its function. In some disorders, such as irritable bowel syndrome (IBS), 5-HT3 receptor inhibitors have been found effective in relieving the symptoms, especially in patients experiencing IBS associated with diarrhoea. STW 5 (Iberogast) has beeen shown to be effective in functional gastrointestinal diseases in several randomiced controlled double blind studies and is widely used in therapy since more than four decades, having a very favourable safety profile. Recent experiments showed that STW 5 was able to decrease 5-HT mediated sensory nerve stimulation in the GIT. It was also shown that it has binding affinities to 5-HT4 and to a lesser extent to 5-HT3 receptors. Our present study was aimed at investigating the possible effects of STW 5 on 5-HT3 receptors of the guinea pig ileum in an attempt to further elucidate its mechanism of action in IBS.

Methods: The response of the isolated guinea pig ileum to the specific 5-HT3 agonist, SR 52772 (3–100µM) was tested in vitro by measuring the contractions evoked by increasing doses of the agonist. The dose response relationship was repeated in the presence of different concentrations of STW 5, applied as an ethanol free lyophilisate, in the bath.

Results: STW 5, in a bath concentration of 1 and 3µg/ml, induced a parallel shift of the dose response curve to SR 52772 to the right. The contraction induced by SR57227 (100µM) was decreased to 77% by STW 5 (1µg/ml) and to 51% by STW 5 (3µg/ml). Effects were statistically significant and indicate an antagonistic effect of STW 5 on 5-HT3 receptors.

Conclusion: The results indicate a possible involvement of 5-HT3 receptor antagonism in the gastrointestinal effects of STW 5 (Iberogast).