The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs
The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs
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DOI：
10.1016/j.ejphar.2010.02.015
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发表时间：
2010-05-25
影响因子：
5
通讯作者：
Lehmann, Anders
中科院分区：
文献类型：
--
作者：
Branden, Lena;Fredriksson, Anita;Lehmann, Anders
虽然有胃食管反流病症状的患者通常对质子泵抑制剂反应良好，但20-30%的患者仍会出现麻烦的症状。在这种情况下，靶向短暂下食管括约肌（LES）松弛的药物可能用作质子泵抑制剂的附加治疗。GABA（B）受体激动剂巴氯芬抑制短暂LES松弛，但由于中枢神经系统活动，它不是理想的药物。Lesogaberan（AZD 3355）是一种外周限制性GABA（B）受体激动剂，具有有限的中枢神经系统活性，可抑制犬的一过性LES松弛。在本研究中，使用24小时pH测定法在犬中研究了lesogaberan（7 μ mol/kg）和巴氯芬（2.8 μ mol/kg）对反流的比较作用。在一天的第一餐前口服药物（或溶剂对照），并计算24小时监测期的反流发作次数（pH= 5 s）和酸暴露时间。平均值（S.E.M.）24 h内反流发作次数，莱索格兰组为4.6次（0.4），巴氯芬组为6.4次（0.6），对照组为10.7次（0.5）（P
While patients with symptoms of gastroesophageal reflux disease generally respond well to proton pump inhibitors, 20-30% continue to experience troublesome symptoms. In such cases, agents that target transient lower esophageal sphincter (LES) relaxation may be useful as add-on therapy to proton pump inhibitors. The GABA(B) receptor agonist baclofen inhibits transient LES relaxation but it is not an ideal agent due to central nervous system activity. Lesogaberan (AZD3355) is a peripherally restricted GABA(B) receptor agonist with limited central nervous system activity that inhibits transient LES relaxation in dogs. In the present study, the comparative effects of lesogaberan (7 mu mol/kg) and baclofen (2.8 mu mol/kg) on reflux were studied in dogs using 24-h pHmetry. Drugs (or vehicle control) were administered orally prior to the first meal of the day, and the number of reflux episodes (pH= 5 s) and acid exposure time were computed for the 24-h monitoring period. The mean (S.E.M.) number of reflux episodes/24 h was 4.6 (0.4) and 6.4 (0.6) for lesogaberan and baclofen, respectively, versus 10.7 (0.5) for control (P