Synergistic and antagonistic pharmacodynamic interaction between ranitidine and cisapride: a study on the isolated rabbit intestine.
The present study examines the pharmacodynamic interaction between the H(2)-receptor antagonist ranitidine and the prokinetic agent cisapride on the isolated rabbit intestine. Ranitidine produced a concentration-dependent contractile effect on the duodenal, ileal and ascending colon preparations, with EC(50)values of 1.35 x 10(-4)M for the duodenum, 1.2 x 10(-4)M for the ileum and 1.15 x 10(-4)M for the ascending colon. The effect of cisapride on the ranitidine contractile effect was dependent on the cisapride concentration used. Thus, cisapride, at concentrations from 10(-10)up to 5 x 10(-7)for the duodenum and the ascending colon and up to 10(-6)M for the ileum, potentiated the contractile responses of the preparations to ranitidine. However, at higher concentrations cisapride produced a non-competitive inhibition of the intestinal contractile responses to ranitidine with IC(50)values of 4.2 x 10(-5)M for the duodenum, 1.65 x 10(-5)M for the ileum and 3.2 x 10(-6)M for the ascending colon. These data show that cisapride may modify the contractile responses of the isolated rabbit intestine to ranitidine, having a potentiating effect up to a certain concentration and an antagonistic one at higher concentrations. In conclusion, co-administration of the above drugs may lead to enhanced or reduced intestinal motility.
Koutsoviti-Papadopoulou
M
M
Department of Pharmacology, Faculty of Veterinary Medicine, Aristotle University, Thessaloniki, Greece. mariakp@vet.auth.gr
Nikolaidis
E
E
Batzias
G C
GC
Kounenis
G
G
D000818:Animals; D020117:Cisapride / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004357:Drug Synergism; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011817:Rabbits; D011899:Ranitidine / Q000494:pharmacology*
D005765:Gastrointestinal Agents; D011899:Ranitidine; D020117:Cisapride