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
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 sp...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131931521X |
| _version_ | 1828413567430295552 |
|---|---|
| author | Takuya Hirata Toshiyuki Funatsu Yoshihiro Keto Shinobu Akuzawa Masao Sasamata Keiji Miyata |
| author_facet | Takuya Hirata Toshiyuki Funatsu Yoshihiro Keto Shinobu Akuzawa Masao Sasamata Keiji Miyata |
| author_sort | Takuya Hirata |
| collection | DOAJ |
| description | 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 ED50(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 1–8h 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. Keywords:: ramosetron, antidiarrheal agent, spasmolytic, conditioned fear stress, normal defecation |
| first_indexed | 2024-12-10T13:12:07Z |
| format | Article |
| id | doaj.art-977af3d157fa49a991e7efd0066a0b42 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T13:12:07Z |
| publishDate | 2008-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-977af3d157fa49a991e7efd0066a0b422022-12-22T01:47:39ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011062264270Inhibitory 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 AgentsTakuya Hirata0Toshiyuki Funatsu1Yoshihiro Keto2Shinobu Akuzawa3Masao Sasamata4Keiji Miyata5Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan; Corresponding author. takuya.hirata@jp.astellas.comApplied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, JapanApplied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, JapanApplied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, JapanApplied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, JapanApplied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, JapanWe 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 ED50(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 1–8h 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. Keywords:: ramosetron, antidiarrheal agent, spasmolytic, conditioned fear stress, normal defecationhttp://www.sciencedirect.com/science/article/pii/S134786131931521X |
| spellingShingle | Takuya Hirata Toshiyuki Funatsu Yoshihiro Keto Shinobu Akuzawa Masao Sasamata Keiji Miyata 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 Journal of Pharmacological Sciences |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.sciencedirect.com/science/article/pii/S134786131931521X |
| work_keys_str_mv | AT takuyahirata inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents AT toshiyukifunatsu inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents AT yoshihiroketo inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents AT shinobuakuzawa inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents AT masaosasamata inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents AT keijimiyata inhibitoryeffectsoframosetronapotentandselective5ht3receptorantagonistonconditionedfearstressinducedabnormaldefecationandnormaldefecationinratscomparativestudieswithantidiarrhealandspasmolyticagents |