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.
Chetty
Navinisha
N
Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Irving
Helen R
HR
Coupar
Ian M
IM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
D011725:Pyridines; D011812:Quinuclidines; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists; C482040:Pumosetrag