A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice
A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice
复制标题
DOI：
10.1002/ejp.798
复制
发表时间：
2016-05-01
影响因子：
3.6
通讯作者：
Vergnolle, N.
中科院分区：
文献类型：
--
作者：
Cenac, N.;Castro, M.;Vergnolle, N.
马来酸曲美布汀是一种对外周和阿片受体具有一定亲和力的非竞争性解痉剂，已被评估为对少数接受无镇静全结肠镜检查的患者的治疗。这种治疗的效率是可比的镇静为基础的结肠镜检查，以减轻疼痛和不适。MethodsA新的和改进的曲美布汀盐能够释放体内硫化氢（H2S），一种气体介质，已知减少伤害，已经开发。该药物盐（GIC-1001）由带有释放H2S的抗衡物（3-硫代氨基甲酰基苯甲酸酯，3 TCB）的曲美布汀组成，后者具有释放H2S的能力。GIC-1001已在这里测试的小鼠模型的结肠直肠expendition.ResultsIn小鼠，而口服曲美布汀（马来酸盐，非H2S-缓冲器）只略有减少伤害性反应，增加结肠直肠扩张的压力，口服GIC-1001（H2S-缓冲器）能够显着减少伤害性反应，所有有害的刺激，在剂量依赖性的方式。GIC-1001的这种效果是显着优于其母体化合物曲美布汀管理在equimolar doses.ConclusionsTaken的效果，这些结果表明增加抗伤害性的性质GIC-1001相比，曲美布汀，这表明该化合物将是一个更好的选择，以减轻内脏疼痛和不适引起的管腔扩张。
BackgroundTrimebutine maleate, a noncompetitive spasmolytic agent with some affinity for peripheral - and -opioid receptors has been evaluated as a treatment in a limited number of patients undergoing sedation-free full colonoscopy. The efficiency of such treatment was comparable to sedation-based colonoscopies to relieve from pain and discomfort.MethodsA new and improved trimebutine salt capable of releasing invivo hydrogen sulphide (H2S), a gaseous mediator known to reduce nociception, has been developed. This drug salt (GIC-1001) is composed of trimebutine bearing a H2S-releasing counterion (3-thiocarbamoylbenzoate, 3TCB), the latter having the ability to release H2S. GIC-1001 has been tested here in a mouse model of colorectal distension.ResultsIn mice, while orally given trimebutine (the maleate salt, non-H2S-releaser) only slightly reduced the nociceptive response to increasing pressures of colorectal distension, oral administration of GIC-1001 (the H2S-releaser) was able to significantly reduce nociceptive response to all noxious stimuli, in a dose-dependent manner. This effect of GIC-1001 was significantly better than the effects of its parent compound trimebutine administered at equimolar doses.ConclusionsTaken together, these results demonstrated increased antinociceptive properties for GIC-1001 compared to trimebutine, suggesting that this compound would be a better option to relieve from visceral pain and discomfort induced by lumenal distension.