Thiophene and its substituted derivatives are very important class of heterocyclic compounds which shows interesting applications in the field of medicinal chemistry. It has made an indispensable anchor for medicinal chemists to produce combinatorial library and carry out exhaustive efforts in the search of lead molecules. It has been reported to possess a wide range of therapeutic properties with diverse applications in medicinal chemistry and material science, attracting great interest in industry as well as academia. It has been proven to be effectual drugs in present respective disease scenario. They are remarkably effective compounds both with respect to their biological and physiological functions such as anti-inflammatory, anti-psychotic, anti-arrhythmic, anti-anxiety, anti-fungal, antioxidant, estrogen receptor modulating, anti-mitotic, anti-microbial, kinases inhibiting and anti-cancer. Thus the synthesis and characterization of novel thiophene moieties with wider therapeutic activity is a topic of interest for the medicinal chemist to synthesize and investigate new structural prototypes with more effective pharmacological activity. However, several commercially available drugs such as Tipepidine, Tiquizium Bromides, Timepidium Bromide, Dorzolamide, Tioconazole, Citizolam, Sertaconazole Nitrate and Benocyclidine also contain thiophene nucleus. Therefore, it seems to be a requirement to collect recent information in order to understand the current status of the thiophene nucleus in medicinal chemistry research.

2008-05-01·Neurogastroenterology & Motility3区 · 医学

Effects of serotonin 5‐HT₃ receptor antagonists on stress‐induced colonic hyperalgesia and diarrhoea in rats: a comparative study with opioid receptor agonists, a muscarinic receptor antagonist and a synthetic polymer

3区 · 医学

Article

作者: Y. Keto ; M. Nakata ; S. Akuzawa ; A. Takeuchi ; K. Miyata ; T. Hirata ; M. Sasamata ; T. Funatsu

Abstract In this study, we examined the effects of serotonin (5‐HT)3 receptor antagonists (5‐HT3RAs) including ramosetron, alosetron, and cilansetron on colonic nociceptive threshold in rats. Furthermore, we established a restraint stress‐induced colonic hyperalgesia model in rats, and compared the inhibitory effects of 5‐HT3RAs on restraint stress‐induced colonic hyperalgesia and diarrhoea with those of loperamide, trimebutine, tiquizium and polycarbophil. The colonic nociceptive threshold was measured as the balloon pressure at the time the rat showed a nociceptive response during colonic distension by an intrarectally inserted balloon. Oral administration of ramosetron (3–30 μg kg−1), alosetron (30–300 μg kg−1), or cilansetron (30–300 μg kg−1) increased the colonic nociceptive threshold in a dose‐dependent manner in non‐stressed rats. Restraint stress for 1 h significantly decreased the colonic nociceptive threshold, but ramosetron (0.3–3 μg kg−1), alosetron (3–30 μg kg−1), cilansetron (3–30 μg kg−1) and trimebutine (100–1000 mg kg−1) significantly inhibited the decrease in the threshold. Loperamide (3–30 mg kg−1), tiquizium (100–1000 mg kg−1) and polycarbophil (1000 mg kg−1) did not affect the restraint stress‐induced decrease in the colonic nociceptive threshold. All drugs tested in this study showed dose‐dependent inhibition of restraint stress‐induced diarrhoea in rats. These results indicate that, unlike existing antidiarrhoeal and spasmolytic agents, 5‐HT3RAs have inhibitory effects on colonic nociception, and prevented restraint stress‐induced both diarrhoea and hyperalgesia at almost the same doses in rats. This suggests that the 5‐HT3RAs may be useful in ameliorating both colonic hyperalgesia and diarrhoea in patients with irritable bowel syndrome.

2008-01-01·Journal of Pharmacological Sciences3区 · 医学

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

3区 · 医学

ArticleOA

作者: Masao Sasamata ; Shinobu Akuzawa ; Takuya Hirata ; Toshiyuki Funatsu ; Yoshihiro Keto ; Keiji Miyata

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.

100 项与替喹溴胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01875	-	A02B	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
十二指肠溃疡	日本	Mylan, Inc.	1984-10-23
胆囊疾病	日本	Mylan, Inc.	1984-10-23
胃炎	日本	Mylan, Inc.	1984-10-23
胃痉挛	日本	Mylan, Inc.	1984-10-23
肠易激综合征	日本	Mylan, Inc.	1984-10-23
肌肉痉挛	日本	Mylan, Inc.	1984-10-23
痉挛	日本	Mylan, Inc.	1984-10-23
胃溃疡	日本	Mylan, Inc.	1984-10-23
尿石症	日本	Mylan, Inc.	1984-10-23