Effect of lesogaberan, a novel GABAB-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects
Effect of lesogaberan, a novel GABAB-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects
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DOI：
10.1111/j.1365-2036.2010.04283.x
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发表时间：
2010-06-01
影响因子：
7.6
通讯作者：
Ruth, M.
中科院分区：
文献类型：
--
作者：
Boeckxstaens, G. E.;Rydholm, H.;Ruth, M.
P>BackgroundTransient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD).AimTo assess the effect of lesogaberan (AZD3355) - a novel peripherally active GABA(B) receptor agonist - on TLESRs.MethodsTwenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of < 7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h after the meal.ResultsTwenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51-0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34-2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18-1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo.ConclusionCompared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.
