Reference

Effect of ramosetron on short-circuit current response in rat colonic mucosa

Effect of ramosetron on short-circuit current response in rat colonic mucosa. Kiso, Tetsuo; Ito, Hiroyuki; Miyata, Keiji (Neuroscience Research, Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305, Japan). European Journal of Pharmacology, 320(2/3), 187-192 (English) 1997 Elsevier. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 We investigated the effects of ramosetron (YM060, (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzi midazole monohydrochloride) on the short-circuit current (Isc) responses to 5-HT receptor agonists in the rat distal colon, and compared its potency to that of other 5-HT3 receptor antagonists. 5-Hydroxytryptamine (5-HT) concn.-dependently increased Isc. The Isc response to 5-HT was partially reduced by tetrodotoxin and ramosetron, and strongly inhibited by GR113808 ([[1-[(2-methylsulfonyl)amino]ethyl]-4-piperidin-yl]methyl 1-methyl-1H-indole-3-carboxylate). 2-Methyl-5-HT and 5-methoxytryptamine also increased Isc. The former response was inhibited by ramosetron, and the latter was abolished by GR113808. Ramosetron, YM114 (KAE-393, (-)-(R)-5-[(1-indolinyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride) and granisetron concn.-dependently antagonized the Isc responses to 2-methyl-5-HT with redn. in the maximal response at higher concns. Apparent pA2 values for these antagonists were 10.40, 10.37 and 8. There are some commonly used reagents like 132036-88-5 in this article.99, resp. Ondansetron produced clear rightward shifts of the concn.-response curves to 2-methyl-5-HT, with a pA2 value of 8.53. These results suggest that 5-HT increases Isc through the 5-HT3 and 5-HT4 receptors, and that ramosetron is a potent and selective 5-HT3 receptor antagonist in rat colonic mucosa. .

Oral formulations of the selective serotonin3 antagonists ramosetron (intraoral disintegrator formulation) and granisetron hydrochloride (standard tablet) in treating acute chemotherapy-induced emesis, nausea, and anorexia: a multicenter, randomized, single-blind, crossover, comparison study

Oral formulations of the selective serotonin3 antagonists ramosetron (intraoral disintegrator formulation) and granisetron hydrochloride (standard tablet) in treating acute chemotherapy-induced emesis, nausea, and anorexia: a multicenter, randomized, single-blind, crossover, comparison study. Feng, Feng Yi; Zhang, Pin; He, You Jian; Li, Yu Hong; Zhou, Mei Zhen; Cheng, Gang; Chen, Yan; Kikkawa, Tomoko; Yamamoto, Minoru (The Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, Peop. Rep. China). Current Therapeutic Research, 63(11), 725-735 (English) 2002 Excerpta Medica, Inc. CODEN: CTCEA9. ISSN: 0011-393X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 63 Background: Chemotherapeutic drugs used to treat cancer may cause nausea and emesis by inducing the release of 5-hydroxytryptamine (5-HT) in the small intestine. Blockage of 5-HT3 receptors in the small intestine by 5-HT3-receptor antagonists might prevent the nausea and vomiting assocd. with chemotherapy for cancer. Objective: The aim of this study was to compare the efficacy and tolerability of the selective 5-HT3 antagonists ramosetron (0.1-mg intraoral disintegrator prepn.) and granisetron hydrochloride (2-mg std. tablet) in the treatment of acute chemotherapy-induced digestive disturbances. Methods: Male and female Chinese cancer patients aged 16 to 74 yr were eligible for this multicenter, randomized, single-blind, crossover, comparison study. Patients were randomized to 1 of 2 treatment groups. Group 1 received 1-time administration of ramosetron 0.1 mg orally without water, followed by a 2-wk washout period after which they received granisetron 2 mg orally with water. Group 2 received granisetron 2 mg orally with water, followed by a 2-wk washout period after which they received ramosetron 0. 15663-27-1 and 132036-88-5 which are cas registry numbers are also used here.1 mg orally without water. Each study drug was administered 1 time, 1 h before infusion of the chemotherapeutic agent. For the efficacy assessment, response data were recorded every 6 h for a total of 24 h after the start of chemotherapy infusion. For the tolerability assessment, adverse events (AEs) were recorded continuously over 24 h. Results: A total of 73 patients (46 males, 27 females; mean age, 49.6 yr [range, 17-70 yr]) were enrolled. Group 1 comprised 37 patients; group 2, 36 patients. Data from 62 (84.9%) patients were used in the efficacy assessment; data from 70 (95.9%) patients were used in the tolerability assessment. The ability of ramosetron to prevent emesis, nausea, and anorexia was similar to that of granisetron during the 0-to-6-h and 0-to-24-h periods following administration of cisplatin or doxorubicin chemotherapy. The tolerability of ramosetron was similar to that of granisetron; AEs were generally mild and transient. Conclusions: In this study, both the intraoral disintegrator formulation of ramosetron and the std. tablet formulation of granisetron were clin. useful for preventing chemotherapy-induced digestive disturbances in cancer patients. .