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• W2046677990 abstract "TRPV1 is a cation channel activated by a range of noxious stimuli and highly expressed in nociceptive fibres. TRPV1 receptors are involved in pain and sensitisation associated with tissue injury and inflammation; hence, TRPV1 antagonists are potentially useful for the treatment of such pain states. SB-705498 is a potent, selective and orally bioavailable TRPV1 antagonist with demonstrated efficacy in a number of preclinical pain models. In this first-time-into-human study, we have investigated the pharmacodynamic and antihyperalgesic activity of SB-705498. The compound was safe and well tolerated at single oral doses up to 400 mg. In a cohort of 19 healthy volunteers, we used a randomised placebo-controlled single-blind cross-over design to assess the effects of SB-705498 (400 mg) on heat-evoked pain and skin sensitisation induced by capsaicin or UVB irradiation. Compared with placebo, SB-705498 reduced the area of capsaicin-evoked flare (P = 0.0047). The heat pain threshold on non-sensitised skin was elevated following SB-705498 (estimated difference from placebo [95% confidence intervals]: 1.3 °C [0.07, 2.53], P = 0.019). Following capsaicin sensitisation, the heat pain threshold and tolerance were similar between SB-705498 and placebo. However, SB-705498 increased heat pain tolerance at the site of UVB-evoked inflammation (estimated difference from placebo: 0.93 °C [0.25, 1.6], P = 0.0054). The magnitude of the pharmacodynamic effects of SB-705498 appeared to be related to plasma concentration. These results indicate that SB-705498, at a clinically safe and well-tolerated dose, has target-specific pharmacodynamic activity in humans. These data provide the first clinical evidence that a TRPV1 antagonist may alleviate pain and hyperalgesia associated with inflammation and tissue injury." @default.
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• W2046677990 date "2007-11-01" @default.
• W2046677990 modified "2023-10-16" @default.
• W2046677990 title "The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans" @default.
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• W2046677990 doi "https://doi.org/10.1016/j.pain.2007.06.006" @default.
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