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

在成人人群中，肠易激综合征（IBS）的患病率约为12%。目前的治疗方法是对症的，并试图减少腹痛和排便紊乱。从基础科学中，我们了解到褪黑激素受体的激动剂可以减缓胃肠道的传输，减少实验性腹痛。这种多模式类型的作用在IBS的治疗中将是非常新颖的，并且将满足未满足的需求。初步的非对照临床试验支持褪黑激素对IBS患者症状的有益作用。在任何进一步的临床研究活动之前，需要对褪黑激素在这种情况下的作用部位和作用模式进行一般表征。缺乏基础科学研究，表征褪黑激素能系统对胃肠道功能的药理学和生理学活性的原理。这里建议的项目将为我们提供迫切需要的相应药理学和生理学特征和澄清，以促进目前可用的信息褪黑激素在肠道中的作用到未来的治疗胃肠道疾病。此外，基本科学概念包括将发现转化为人体组织的形态学和药理学。总体概念是提供机制概念，促进我们对肠道中褪黑激素能控制的知识转化为临床试验，并帮助相应的临床研究设计和从功能性胃肠道疾病（如IBS）患者中选择患者。

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.