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• W2088510881 abstract "Background RS-127445 is a selective, high affinity 5-HT2Breceptor antagonist. We investigated whether 5-HT2Breceptor antagonists can reduce colonic visceral hypersensitivity caused by restraint stress or by proximal colonic inflammation. Methods Visceral hypersensitivity was induced in rats by either restraint stress or injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon. Restraint stress produced a significant increase in numbers of abdominal contractions evoked by colorectal distension (CRD), measured as a quantitative index of visceral nociception in rats. Seven days after TNBS injection, the pain threshold to CRD at the non-inflamed distal colon, that was determined as the minimum pressure required to evoke abdominal cramp, was significantly decreased. The effect of RS-127445 on visceral hypersensitivity was assessed in either naïve or TNBS-treated rats. Key Results Oral administration of a selective, high affinity 5-HT2Breceptor antagonist, RS-127445, significantly inhibited visceral hypersensitivity provoked by restraint stress (35 to 74% inhibition at 1 to 10 mg kg−1). Oral RS-127445 produced a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg kg−1), although it was without significant effect on the visceral nociceptive threshold of naïve rats. RS-127445 (1 to 30 mg kg−1, p.o.) also dose-dependently reduced the restraint stress-induced defecation in naïve and TNBS-treated rats. Conclusions & Inferences These results suggest that 5-HT2Breceptors are involved in signaling from the colon in rats in which there is visceral hypersensitivity and that a selective 5-HT2Breceptor antagonist could have therapeutic potential for the treatment of gut disorders characterized by visceral hypersensitivity." @default.
• W2088510881 created "2016-06-24" @default.
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• W2088510881 date "2010-02-01" @default.
• W2088510881 modified "2023-10-16" @default.
• W2088510881 title "A selective, high affinity 5-HT_2Breceptor antagonist inhibits visceral hypersensitivity in rats" @default.
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• W2088510881 doi "https://doi.org/10.1111/j.1365-2982.2009.01395.x" @default.
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