Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs.
Neurogastroenterol Motil
; 24(6): 566-74, e256, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-22429221
ABSTRACT
UNLABELLED BACKGROUND Acotiamide hydrochloride (acotiamide), a novel selective acetylcholinesterase (AChE) inhibitor, has proven significantly effective in treating functional dyspepsia (FD) in clinical trials, particularly in alleviating meal-related symptoms. In the present study, we examined the gastrointestinal prokinetic effects of acotiamide administered orally or intraduodenally in conscious dogs and investigated in vivo and ex vivo anti-AChE activity of acotiamide to clarify its mechanism of prokinetic action. METHODS:
Gastrointestinal motility was measured in conscious dogs with chronically implanted force transducers. KEYRESULTS:
Oral administration of acotiamide stimulated postprandial gastroduodenal and colonic motor activities. Measurement of gastrointestinal motility showed that acotiamide, like itopride and mosapride, enhanced gastric antral motility. Further, acotiamide markedly improved clonidine (an α(2) -adrenoceptor agonist)-induced hypomotility in a dog model of gastric motor dysfunction. The postprandial gastric antral motility enhanced by acotiamide was completely abolished on treatment with the muscarinic receptor antagonist atropine. Results of an in vivo experiment on anti-AChE activity showed clearly increased acetylcholine-induced gastric motility on intraduodenal administration of acotiamide, just as observed with the AChE inhibitor neostigmine. Further, in ex vivo experiment, intraduodenal administration of acotiamide significantly inhibited AChE activity in canine gastric antrum. CONCLUSIONS & INFERENCES Our findings revealed that acotiamide administered through the alimentary tract exerts gastroprokinetic action via cholinergic pathways by inhibiting AChE activity. These results may also confirm the mechanism of action in clinical efficacy of acotiamide on FD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tiazoles
/
Benzamidas
/
Inhibidores de la Colinesterasa
/
Tracto Gastrointestinal
/
Vaciamiento Gástrico
/
Motilidad Gastrointestinal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurogastroenterol Motil
Asunto de la revista:
GASTROENTEROLOGIA
/
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón