A Clinical Trial of Trimebutine (Mebutin) in Spastic Colon

Moshal, M G; Herron, Malcolm

doi:10.1177/030006057900700311

Cited by 83 publications

(35 citation statements)

References 5 publications

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“…On the contrary, it has been reported to decrease the meal-induced sigmoid hypermotility (38) and to increase the number of propagated spike bursts (39) in constipated IBS patients. Two double-blind, placebo controlled studies reported that trimebutine oral administration for up to two months significantly improved clinical symptoms and shortened colonic transit time in constipated IBS patients (39,40).…”

Section: Opioid Treatment Of Functionalmentioning

confidence: 99%

Role of Opioid Ligands in the Irritable Bowel Syndrome

Corazziari

1999

Canadian Journal of Gastroenterology and Hepatology

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E Corazziari. Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol 1999;13(Suppl A):71A-75A. Endogenous opioid peptides -enkephalins, beta-endorphin and dynorphins -are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists -morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide -have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials. Le rôle des ligands des récepteurs des opiacés dans le syndrome du côlon irritable RÉSUMÉ : Les peptides opiacés endogènes, les encéphalines, bêta-endorphines et dynorphines, sont localisés en certains points spécifiques du cerveau, de la moelle épinière, des ganglions autonomes et du système nerveux entérique. Les opiacés endogènes participent à la régulation de l'afférence et de la sensibilité viscérale nerveuse, de même qu'à diverses fonctions motrices viscérales induites par le système nerveux central et par les réflexes entéro-entériques et myo-entériques. Leur effet final sur la physiologie intestinale est l'équilibre harmonieux de leurs liaisons aux sous-types de récepteurs des opiacés mu, delta et kappa. Des ligands des récepteurs des opiacés exogènes présentant des affinités diverses à l'endroit des sous-types de récepteurs des opiacés ont été mis à profit utilement pour modifier et normaliser les anomalies de la fonction intestinale. Le...

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Section: Opioid Treatment Of Functionalmentioning

confidence: 99%

Role of Opioid Ligands in the Irritable Bowel Syndrome

Corazziari

1999

Canadian Journal of Gastroenterology and Hepatology

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“…Trimebutine is effective for various symptoms including abdominal pain, nausea and IBS (26). The usual dose of trimebutine inhibits cholinergic and adrenergic neurons by activating the opiate-m and k receptors, resulting in a dual effect on intestinal motility (27,28).…”

Section: Discussionmentioning

confidence: 99%

Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats

Saito

Mizutani

Iwanaga

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the laxative and anti-diarrheal activity of polycarbophil, an insoluble hydrophilic polymer, in comparison with other agents used for treating functional bowel disorder (FBD). In naive rats, polycarbophil (500 mg /kg) increased fecal weight and water contents without producing diarrhea. Carboxymethylcellulose (CMC) did not produce evident changes in bowel movement. Picosulfate markedly produced diarrhea. Loperamide, trimebutine and granisetron decreased stool output dose-dependently. Constipation, indicated by decrease in fecal weight, was produced by loperamide and clonidine in rats. Polycarbophil (500 mg /kg) and CMC increased fecal weight without diarrhea. Conversely trimebutine further decreased fecal weight in constipated rats. Polycarbophil (500 mg /kg) suppressed diarrhea induced by castor oil, and at 250 -500 mg /kg, it produced shaped stools in animals with stools loosened by prostaglandin E2, serotonin or carbachol in mice. Polycarbophil (500 mg /kg) also reduced stools in rats with stool output increased by wrap restraint stress (WRS). CMC had no effect in the diarrhea models, except for carbachol-induced diarrhea, and WRS-induced evacuation. Loperamide, trimebutine and granisetron inhibited diarrhea production and WRS-induced evacuation, except for carbachol-induced diarrhea. The results show that polycarbophil prevents constipation and diarrhea without inducing diarrhea or constipation, which is different from the other agents. Hydrophilic polymers such as polycarbophil will be promising agents for the treatment of FBD.

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“…The efficacies of TM-906 in spastic colon (1,2) and in recovery of the digestive transit time after abdominal surgery (3) were supposed to due to the inhibitory and stimulatory effects of TM-906 on intestinal motility. It has been reported that TM-906 produces an excitation of the spontaneous contraction of the isolated guinea pig colon in preparations with low tone, while it causes an inhibition of the spontaneous contraction in preparations with high tone, and it was suggested that these effects of TM-906 are due to its direct action on smooth muscles (4).…”

Section: Abstract-effectsmentioning

confidence: 99%

Effects of Trimebutine Maleate (TM-906) on the Spontaneous Contraction of Isolated Duodenum and Ileum in Both Guinea Pigs and Rabbits

Takenaga¹,

Magaribuchi²,

Tamaki³

1986

Japanese Journal of Pharmacology

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Abstract-Effectsof trimebutine maleate (TM-906) on the spontaneous contraction of isolated duodenum and ileum were studied in both guinea pigs and rabbits. In the duodenum and ileum of both guinea pigs and rabbits, TM-906 (10-6 g/ml, 10-5 g/ml) produced a potentiation of the spontaneous contraction in preparations with low contractile activity (low tone or small contraction), while it caused an inhibition of the spontaneous contraction in preparations with high contractile activity (high tone or large contraction).The potentiation of spontaneous con traction by TM-906 was more pronounced in the ileum than in the duodenum of both guinea pigs and rabbits. When the spontaneous contraction of duodenum and ileum was decreased by atropine, the potentiation of spontaneous contraction by TM-906 was further augmented and was more pronounced in the ileum than in the duodenum.When the spontaneous contraction was remarkably poten tiated by physostigmine or acetylcholine, TM-906 markedly inhibited the poten tiated spontaneous contraction, and the potentiation by TM-906 seen in pre parations with low contractile activity disappeared. From these results, it is concluded that TM-906 produces, depending on the contractile activity of the preparations, a potentiation or an inhibition of the spontaneous contraction of duodenum and ileum in both guinea pigs and rabbits and that the potentiation by TM-906 is more pronounced in the ileum than in the duodenum. It is suggested that the endogeneous acetylcholine partly modifies the effects of TM-906, but that it does not relate to the more pronounced potentiation by TM-906 in the ileum than in the duodenum.

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A Clinical Trial of Trimebutine (Mebutin) in Spastic Colon

Cited by 83 publications

References 5 publications

Role of Opioid Ligands in the Irritable Bowel Syndrome

Role of Opioid Ligands in the Irritable Bowel Syndrome

Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats

Effects of Trimebutine Maleate (TM-906) on the Spontaneous Contraction of Isolated Duodenum and Ileum in Both Guinea Pigs and Rabbits

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