Effects of the novel 5-HT3 agonist MKC-733 on the rat, mouse and guinea pig digestive tract

The contractile activity of the novel 5-HT(3) receptor agonist MKC-733 was determined in intestinal tissues of rats, guinea pigs and mice. The potential influence of non-5-HT(3) receptors was removed by the inclusion of methysergide and GR125487. MKC-733 had a lower efficacy than 5-HT in the rat jejunum, ileum and distal colon; however, it had similar efficacy and potency to 5-HT in the rat proximal colon. The activity profile of MKC-733 was different in the guinea pig intestine where it exhibited greater potency and efficacy than 5-HT in all regions. MKC-733 showed little to no response in the regions of the mouse intestine. Responses to MKC-733 in the rat and guinea pig tissues were inhibited by ondansetron, confirming its action on 5-HT(3) receptors. These in vitro studies indicate that MKC-733 displays both regional and species specificities.