Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

Abstract

Background/AimsA selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit.MethodsMale guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm).ResultsThe average charcoal transit was 51.3 ± 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 ± 21.9%, 46.9 ± 9.14% and 8.4 ± 5.6% of the total small intestine at the concentrations of 10, 30 and 100 µg/kg, respectively. GI transit after administration of TRH (100 µg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 ± 9.22%; TRH, 73.4 ± 14.7%; MO, 81.0 ± 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO.ConclusionsRamosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.

Is Ramosetron Really Useful to Treat Diabetic Diarrhea With Rapid Small Bowel Transit?

“…Table shows the summary of clinical features of 2 cases with refractory diabetic diarrhea successfully treated with ramosetron. These findings are consistent with the study by Park et al,1 in which ramosetron inhibited accelerated upper GI transit in male guinea pigs. A recent animal study showed that ramosetron improved soybean oil- and corticotropin releasing factor-induced delay in gastric emptying of rats 4.…”

“…TO THE EDITOR: I read with interest the study by Park et al1 regarding inhibitory effect of ramosetron on accelerated upper gastrointestinal (GI) transit of male guinea pigs. In the study, GI transit was assessed as the migration of charcoal mixture from the pylorus to the most distal point of migration and expressed as a percentage of charcoal migration through the total length of small intestine.…”

Is Ramosetron Really Useful to Treat Diabetic Diarrhea With Rapid Small Bowel Transit?: Author's Reply

“…In our study, the effect was well demonstrated by its inhibitory effects on accelerated GI transit caused by 5-HT, thyrotropin-releasing hormone and mustard oil 3. However, Hirata et al4 showed recently that ramosetron significantly inhibited the delayed gastric emptying in a corticotrophin releasing factor and soybean oil-induced rat model, in comparison with anti-diarrheal agent and spasmolytics.…”

“…An imbalance between the inhibitory and excitatory ENS could be one of the causes of diabetic diarrhea. The 5-HT 3 receptor antagonist inhibits the excitatory neurons of ENS thus plays a role in regulating a balance of the ENS components in diabetic patients 2,3. Based on these mechanisms, Murao and Hosokawa2 reported the effect of ramosetron, which was developed as an antiemetic drug for cancer chemotherapy and for the treatment of diabetic diarrhea.…”

“…There were conflicting results from animal experiments on the same drug 3,4. This could be an evidence presenting the different treatment effects of ramosetron in patients with autonomic neuropathy, diabetic diarrhea and gastroparesis.…”