Cisapride reverses the anticholinergic effect of disopyramide on the isolated guinea-pig urinary bladder.
The present investigation aims to examine whether the prokinetic agent cisapride is able to reverse disopyramide's anticholinergic effect on the isolated guinea-pig urinary bladder. Acetylcholine, at concentrations ranging from 10(-7) to 10(-3) M, produced a stimulatory effect on the urinary bladder (pEC(50) value=5.1). Disopyramide competitively antagonized the contractile effect of acetylcholine with an ID(50)=4.4 x 10(-6) M. Although cisapride by itself had either no intrinsic contractile action or a modest effect on the urinary bladder, at concentrations ranging from 3 x 10(-7) to 10(-6) M, it significantly reversed the above inhibitory effect of disopyramide, and produced a parallel leftward shift of the concentration-response curve for acetylcholine in the presence of disopyramide. The pEC(50) values for acetylcholine in the presence of 3 x 10(-6) M and 10(-5) M disopyramide were 4.7 and 4.2, respectively, while in the presence of 10(-5) M disopyramide, after pretreatment with 5 x 10(-7) M cisapride, the pEC(50) value for acetylcholine was 4.6. It is concluded that cisapride is effective in reversing the anticholinergic activity of disopyramide on the isolated guinea-pig urinary bladder, probably by facilitating cholinergic neurotransmission.
Koutsoviti-Papadopoulou
M
M
Department of Pharmacology, School of Veterinary Medicine, Aristotle University, Thessaloniki 540 06, Greece. mariakp@vet.auth.gr
Nikolaidis
E
E
Batzias
G C
GC
Kounenis
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D020117:Cisapride / Q000008:administration & dosage / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects*
D018680:Cholinergic Antagonists; D005765:Gastrointestinal Agents; D010276:Parasympatholytics; D004206:Disopyramide; D000109:Acetylcholine; D020117:Cisapride