title: R 50 595, a selective non-competitive antagonist of cisapride, BRL 24924 and 5-hydroxytryptamine on the guinea-pig ileum.
abstract: 5-Hydroxytryptamine and substituted benzamides such as cisapride and BRL 24924 enhance the twitch responses of the electrically stimulated longitudinal muscle-myenteric plexus preparation of the guinea-pig. The effects of these benzamides and 5-HT could possibly be mediated via similar receptor-effector systems. The aim of our study was therefore to determine whether R 50 595, an analogue of cisapride devoid of intrinsic activity, could specifically interfere with the effects of cisapride and BRL 24924 and if so, whether it would also affect the responses to serotonin. R 50 595 had no effect on the twitch responses of the electrically stimulated preparation up to a concentration of 3 X 10(-7) M. Cisapride and BRL 24924 both enhanced the contractile response to electrical stimulation by a maximum of 37 +/- 7% at 3 X 10(-7) M for cisapride and 36 +/- 6% for BRL 24924, also at 3 X 10(-7) M. R 50 595 (10(-7)(-3) X 10(-7) M) antagonized the effects of cisapride and BRL 24924 in a non-competitive way. 5-HT enhanced the contractile responses by a maximum of 24 +/- 3.2% at 3 X 10(-8) M. The effects of 5-HT were completely abolished at a concentration of 3 X 10(-7) M R 50 595. R 50 595 also antagonized the effects of 5-HT in a non-competitive way.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: NIDDR, University of Utrecht, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Van den Brink
authors.forename: J A
authors.initials: JA
authors.lastname: Schuurkes
authors.forename: J M
authors.initials: JM
authors.lastname: Van Nueten
authors.forename: J M
authors.initials: JM
authors.lastname: Van Rossum
mesh_terms: D000818:Animals; D001549:Benzamides / Q000037:antagonists & inhibitors*; D001643:Bridged Bicyclo Compounds / Q000037:antagonists & inhibitors*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000037:antagonists & inhibitors*; D020117:Cisapride; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010880:Piperidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D012702:Serotonin Antagonists
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D010880:Piperidines; D012702:Serotonin Antagonists; C065433:R 50595; C053006:renzapride; D020117:Cisapride