Effect of ramosetron on conditioned emotional stress-induced colonic dysfunction as a model of irritable bowel syndrome in rats

Funatsu, Toshiyuki; Takeuchi, Asako; Hirata, Tetsuya; Keto, Yoshihiro; Akuzawa, Shinobu; Sasamata, Masao

doi:10.1016/j.ejphar.2007.06.041

Cited by 24 publications

(21 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The model is widely used for the evaluation of anxiolytic, antidepressant, and anti-IBS agents (12,14). In this model, we found that all test compounds including ramosetron, loperamide, trimebutine, and tiquizium inhibited CFSinduced defecation in a dose-dependent manner, with the potency (based on a comparison of ED 50 values) decreasing in the order ramosetron>>loperamide>>tiquizium> trimebutine.…”

Section: Discussionmentioning

confidence: 96%

“…This experiment was performed according to the method of Funatsu et al (12). Using an electric-shock machine (CB2000; O'Hara, Inc., Tokyo) with an electrode grid-inlaid floor (17 × 17 × 39 cm), a maximal 2 mA of electric current and illumination with three 40 W electric bulbs were applied to rats for 5 s per min, with a total of 15 exposures in each session.…”

Section: Conditioned Fear Stress-induced Defecation In Ratsmentioning

confidence: 99%

“…Ramosetron is also known to potently inhibit stress-induced abnormal defecation in animals (12,13) and is currently under development for use in patients suffering from IBS-D. No study, however, has directly analyzed the inhibitory effects of ramosetron on stress-induced abnormal defecation, in comparison with existing drugs prescribed for IBS-D.…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, therefore, we examined the effect of ramosetron on stress-induced abnormal defecation using a rat model of conditioned fear stress (CFS), which is known to be psychological stress model useful for the evaluation of anxiolytic, antidepressant, and anti-IBS agents (12,14), and compared ramosetron with the antidiarrheal and spasmolytic agents such as loperamide, trimebutine (opioid receptor agonist), and tiquizium (muscarinic receptor antagonist). In addition, because certain antidiarrheal and spasmolytic agents have been reported to simultaneously improve the symptoms of IBS and cause severe constipation (15,16), we also evaluated the influence of these drugs on normal (nonstressed) defecation in rats.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

et al. 2008

Self Cite

View full text Add to dashboard Cite

Abstract. We examined the effect of ramosetron, a potent serotonin (5-HT) 3 -receptor antagonist for irritable bowel syndrome with diarrhea, on conditioned fear stress (CFS)-induced defecation and normal (non-stressed) defecation in rats and compared ramosetron with the antidiarrheal agent loperamide and the spasmolytic agents trimebutine and tiquizium. Ramosetron, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation in a dose-dependent manner with ED 50 (95% confidence limit) values of 0.019 (0.01 -0.028), 9.4 (4.0 -22), 850 (520 -2,400), and 300 (190 -450) mg/ kg, respectively. A significant effect of ramosetron on CFS-induced defecation appeared at 10 min after dosing and was sustained for 8 h. In contrast, loperamide, trimebutine, and tiquizium significantly inhibited CFS-induced defecation between 1 -8, 1 -4, and 1 -8 h after administration, respectively. High doses of ramosetron did not affect normal defecation, whereas loperamide, trimebutine, and tiquizium significantly inhibited this process. In conclusion, ramosetron has potent, rapid-onset, and long-lasting inhibitory effects on CFS-induced defecation in rats, but does not influence normal defecation. The present findings indicate that ramosetron will be a useful therapeutic agent for irritable bowel syndrome with diarrhea, showing greater efficacy and safety than other antidiarrheal and spasmolytic agents.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Conditioned Fear Stress-induced Defecation In Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preliminary pharmacokinetic data suggest that it has a greater affinity, slower dissociation, and stronger antagonism at the 5-HT3 receptor than either alosetron or cilansetron [54] . It also appears to be superior to both of these medications in inhibiting stress-induced defecation and stress-induced changes in colonic transit rates in rats [54,55] . Data in human use are not available but can be anticipated in the near future.…”

Section: -Ht3 Antagonistsmentioning

confidence: 98%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

show abstract

Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects

Asadi-Shahmirzadi

Mozaffari

Sanei

et al. 2012

Chin. J. Integr. Med.

View full text Add to dashboard Cite

OBJECTIVE: To evaluate the beneficial effects of a mixture of Aloe vera (AV) and Matricaria recutita (German chamomile, GC) in an experimental model of irritable bowel syndrome (IBS). METHODS: IBS was induced by a 5-day restraint stress in rats including the groups of control (water), GC (300 mg/kg), loperamide (10 mg/kg), mixed AV and GC (50: 50 at doses of 150, 300 or 450 mg/kg assigned as Mix-150, Mix-300 and Mix-450, respectively) and the sham group which did not receive any restraint stress and was fed with saline. All medications were administered intragastrically by gavage for 7 days, 2 days as pre-treatment followed by 5 days during induction of IBS every day before restraining. RESULTS: The increased tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO) activity, and lipid peroxidation (LPO) in colonic cells in the control group were significantly decreased in the treatment groups. GC inhibited only small bowel transit while the AV/GC mixture delayed gastric emptying at the doses of 150 and 300 mg/kg. The AV/GC mixture also reduced colonic transit and small bowel transit at the dose of 150 mg/kg. CONCLUSIONS: The severity of stress-induced IBS was diminished by the AV/GC mixture at all doses used but not dose-dependently, via inhibiting colonic MPO activity and improving oxidative stress status. The effect of the mixture was more effective than GC alone. The present results support effectiveness of the AV and GC combination in IBS.

show abstract

Effect of ramosetron on conditioned emotional stress-induced colonic dysfunction as a model of irritable bowel syndrome in rats

Cited by 24 publications

References 19 publications

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT3–Receptor Antagonist, on Conditioned Fear Stress–Induced Abnormal Defecation and Normal Defecation in Rats: Comparative Studies With Antidiarrheal and Spasmolytic Agents

Updates on treatment of irritable bowel syndrome

Benefit of Aloe vera and Matricaria recutita mixture in rat irritable bowel syndrome: Combination of antioxidant and spasmolytic effects

Contact Info

Product

Resources

About