Yang Hong, Ma Tonghui
Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, School of Life Sciences, Liaoning Normal UniversityDalian, China.
Institute of Traditional Chinese Medicine, Nanjing University of Chinese MedicineNanjing, China.
Front Pharmacol. 2017 Jun 30;8:418. doi: 10.3389/fphar.2017.00418. eCollection 2017.
Constipation is one of the most frequently reported gastrointestinal (GI) disorders that negatively impacts quality of life and is associated with a significant economic burden to the patients and society. Traditional treatments including lifestyle modification and laxatives are often ineffective in the more severe forms of constipation and over the long term. New medications targeting at intestinal chloride channels and colonic serotonin receptors have been demonstrated effective in recent years. Emerging agents focusing on improving intestinal secretion and/or colonic motility have been shown effective in animal models and even in clinical trials. Recognization of the role of cystic fibrosis transmembrane regulator (CFTR) and calcium-activated chloride channels (CaCCs) in intestine fluid secretion and motility modulation makes CFTR and CaCCs promising molecule targets for anti-constipation therapy. Although there are multiple choices for constipation treatment, there is still a recognized need for new medications in anti-constipation therapy. The present review covers the discovery of luminally acting agents for constipation treatment described in both patents (2011-present) and scientific literatures.
便秘是最常报告的胃肠道疾病之一，对生活质量有负面影响，并给患者和社会带来巨大经济负担。包括生活方式改变和泻药在内的传统治疗方法，对于更严重形式的便秘以及长期治疗往往无效。近年来，针对肠道氯离子通道和结肠5-羟色胺受体的新型药物已被证明有效。专注于改善肠道分泌和/或结肠动力的新型药物在动物模型甚至临床试验中已显示出疗效。认识到囊性纤维化跨膜传导调节因子（CFTR）和钙激活氯离子通道（CaCCs）在肠道液体分泌和动力调节中的作用，使CFTR和CaCCs成为抗便秘治疗有前景的分子靶点。尽管便秘治疗有多种选择，但抗便秘治疗中对新型药物仍有公认的需求。本综述涵盖了专利（2011年至今）和科学文献中描述的用于便秘治疗的腔内作用药物的发现。
