Melatonin receptor agonists, potential drugs for the treatment of irritable bowel syndrome (IBS)

在成人中，肠易激综合征(IBS)的患病率约为12%。目前的治疗方法是有症状的，并试图减少腹痛和肠道运动障碍。从基础科学中我们了解到，褪黑素受体的激动剂可以减缓胃肠传输，减轻实验性腹痛。这种多模式类型的行动在治疗IBS方面将是非常新颖的，并将满足未得到满足的需求。初步的非对照临床试验支持褪黑素对IBS患者症状的有益影响。在任何进一步的临床研究活动之前，需要对褪黑素在这方面的作用部位和作用方式进行总体描述。缺乏基础科学研究来描述褪黑素能系统对胃肠功能的药理和生理活性原理。这项建议的项目将为我们提供迫切需要的各自的药理学和生理学特征和澄清，以促进目前可用的褪黑激素在肠道中的作用信息，用于未来的胃肠道疾病治疗。此外，基本的科学概念包括将发现转化为人体组织的形态和药理学转换。最重要的概念是提供机械概念，便于将我们在肠道中关于褪黑激素能控制的知识转化为临床试验，并帮助从IBS等功能性胃肠疾病患者中分别进行临床研究设计和患者选择。

In the adult population irritable bowel syndrome (IBS) has a prevalence of ~12%. Current therapeutic approaches are symptomatic and attempt to reduce abdominal pain and disturbed bowel movements. From basic science we learned that agonists at the melatonin receptors slow down gastrointestinal transit and reduce experimental abdominal pain. Such a multimodal type of action would be extremely novel in the treatment of IBS and would meet unmet needs. Preliminary uncontrolled clinical trials support a beneficial effect of melatonin on symptoms of patients with IBS. A general characterisation of site of action and mode of action of melatonin in this context needs to be done prior to any further clinical study activity. There is a lack of basic science studies characterizing principles of pharmacological and physiological activity of the melatoninergic system on gastrointestinal function. The here suggested project will provide us with the respective pharmacological and physiological characterisations and clarifications that are urgently needed in order to promote the currently available information of melatonin action in the gut into future treatment in gastrointestinal disease. Furthermore the basic science concept includes morphological and pharmacological translation of the findings into human tissue. The overarching concept is to provide mechanistic concepts that facilitate the translation of our knowledge on melatoninergic control in the gut into clinical trials and help with respective clinical study design and patient selection from patients with functional gastrointestinal disorders like IBS.