General pharmacology of the four gastrointestinal motility stimulants bethanechol, metoclopramide, trimebutine, and cisapride.
The pharmacological profile of bethanechol (CAS 674-38-4), metoclopramide (CAS 364-62-5), trimebutine (CAS 39133-31-8) and cisapride (CAS 81098-60-4) was studied in a series of simple pharmacological tests in rats and dogs. Bethanechol stimulated both gastric emptying and intestinal propulsion but displayed also the well-known behavioral effects of a direct muscarinic acetylcholine receptor agonist. Metoclopramide showed the profile of a centrally active dopamine D2 antagonist. In addition, metoclopramide displayed a stimulant effect on spontaneous gastric emptying in rats, an effect that could not be related to dopamine D2 antagonism. The only effect observed with trimebutine was protection from castor oil diarrhea, probably due to its reported interaction with peripheral opiate receptors. Cisapride was a potent stimulant of gastric emptying in rats, 7 times more potent than metoclopramide. Cisapride was also a very specific gastrokinetic, over a large dose range (specificity ratio: greater than or equal to 20) devoid of effects indicative for direct interaction with dopamine or acetylcholine receptors. The relationship between the differential activity profiles of the compounds in the present study and differences in their mechanism of action and side-effect liability is discussed.
Department of Pharmacology, Janssen Research Foundation, Beerse, Belgium.
A A
AA
Megens
F H
FH
Awouters
C J
CJ
Niemegeers
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001626:Bethanechol Compounds / Q000494:pharmacology; D020117:Cisapride; D003216:Conditioning, Operant / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D004285:Dogs; D005746:Gastric Emptying / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008787:Metoclopramide / Q000494:pharmacology; D009043:Motor Activity; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D014287:Trimebutine / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D001626:Bethanechol Compounds; D005765:Gastrointestinal Agents; D010880:Piperidines; D012702:Serotonin Antagonists; D008787:Metoclopramide; D001058:Apomorphine; D014287:Trimebutine; D020117:Cisapride