Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT_3-Receptor Antagonist, on Conditioned Fear Stress-Induced Abnormal Defecation and Normal Defecation in Rats : Comparative Studies With Antidiarrheal and Spasmolytic Agents
スポンサーリンク
概要
- 論文の詳細を見る
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 – 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.
- 社団法人 日本薬理学会の論文
- 2008-02-20
著者
-
SASAMATA Masao
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
-
MIYATA Keiji
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
-
Miyata Keiji
Applied Pharmacology Res. Laboratories Drug Discovery Res. Astellas Pharma Inc. Jpn
-
Miyata Keiji
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
Sasamata Masao
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
Hirata Takuya
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
Akuzawa Shinobu
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
FUNATSU Toshiyuki
Applied Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd.
-
KETO Yoshihiro
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma, Inc.
-
Keto Yoshihiro
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
Funatsu Toshiyuki
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
-
Funatsu Toshiyuki
Applied Pharmacology Laboratories Yamanouchi Pharmaceutical Co. Ltd.
-
Sasamata Masao
Applied Pharmacology Res. Laboratories Drug Discovery Res. Astellas Pharma Inc.
-
Miyata Keiji
Applied Pharmacology Res. Laboratories Drug Discovery Res. Astellas Pharma Inc.
関連論文
- New Topics in Vasopressin Receptors and Approach to Novel Drugs : Research and Development of Conivaptan Hydrochloride (YM087), a Drug for the Treatment of Hyponatremia
- Pharmacological Characterization of a New Antimuscarinic Agent, Solifenacin Succinate, in Comparison with Other Antimuscarinic Agents(Pharmacology)
- Effects of Intravenously and Orally Administered Solifenacin Succinate (YM905) on Carbachol-Induced Intravesical Pressure Elevation and Salivary Secretion in Mice(Pharmacology)
- The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Ameliorative Effect of Solifenacin Succinate (Vesicare®), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especially Urge
- Relationship between the Functional Effect of Tamsulosin and Its Concentration in Lower Urinary Tract Tissues in Dogs(Pharmacology)
- YM866, a Novel Modified Tissue-Type Plasminogen Activator, Affects Left Ventricular Function and Myocardial Infarct Development in Dogs With Coronary Artery Thrombi
- Enzymologic and Pharmacologic Profile of Loxoprofen Sodium and Its Metabolites(Pharmacology)
- A Novel Vasopressin Dual V_/V_2 Receptor Antagonist, Conivaptan Hydrochloride, Improves Hyponatremia in Rats with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)(Pharmacology)
- Inhibitory Effects of Ramosetron, a Potent and Selective 5-HT_3-Receptor Antagonist, on Conditioned Fear Stress-Induced Abnormal Defecation and Normal Defecation in Rats : Comparative Studies With Antidiarrheal and Spasmolytic Agents
- Micro-CT imaging analysis for the effect of celecoxib, a cyclooxygenase-2 inhibitor, on inflammatory bone destruction in adjuvant arthritis rats
- Evaluation of the Pharmacological Profile of Ramosetron, a Novel Therapeutic Agent for Irritable Bowel Syndrome
- The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction : Ameliorative Effect of Solifenacin Succinate (Vesicare^【○!R】), a Bladder-Selective Antimuscarinic Agent, on Overactive Bladder Symptoms, Especiall
- Tamsulosin Potently and Selectively Antagonizes Human Recombinant .ALPHA.1A/1D-Adrenoceptors: Slow Dissociation from the .ALPHA.1A-Adrenoceptor May Account for Selectivity for .ALPHA.1A-Adrenoceptor over .ALPHA.1B-Adrenoceptor Subtype
- Tacrolimus Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice: Implication of Interferon-.GAMMA. and Interleukin-1.BETA. Suppression