Sarna Sushil K
Division of Gastroenterology, Dept. of Internal Medicine, University of Texas Medical Branch at Galveston, 9.138 Medical Research Bldg., Galveston, TX 77555-1064, USA.
Am J Physiol Gastrointest Liver Physiol. 2006 Oct;291(4):G545-55. doi: 10.1152/ajpgi.00122.2006. Epub 2006 Mar 24.
The science of gastrointestinal motility has made phenomenal advances during the last fifty years. Yet, there is a paucity of effective promotility drugs to treat functional bowel disorders that affect 10-29% of the U.S. population. A part of the reason for the lack of effective drugs is our limited understanding of the etiology of these diseases. In the absence of this information, mostly an ad hoc approach has been used to develop the currently available drugs, which are modestly effective or effective in only a subset of the patients with functional bowel disorders. This review discusses a grounds-up approach for development of the next generation of promotility drugs. The approach is based on our current understanding of 1) the different types of contractions that produce overall motility function of mixing and orderly net distal propulsion in major gut organs, 2) the regulatory mechanisms of these contractions, 3) which receptors and intracellular signaling molecules could be targeted to stimulate specific types of contractions to accelerate or retard transit, and 4) the strengths and limitations of animal models and experimental approaches that could screen potential promotility drugs for their efficacy in human gut propulsion in functional bowel disorders.
在过去的五十年里，胃肠动力科学取得了惊人的进展。然而，用于治疗功能性肠道疾病的有效促动力药物却很匮乏，这类疾病影响着10%至29%的美国人口。缺乏有效药物的部分原因是我们对这些疾病病因的了解有限。由于缺乏这方面的信息，目前可用的药物大多是通过临时的方法开发出来的，这些药物仅对部分功能性肠道疾病患者有一定效果或有效。这篇综述讨论了一种全新的方法来开发下一代促动力药物。该方法基于我们目前对以下方面的理解：1）在主要肠道器官中产生混合和有序净向远端推进的整体动力功能的不同类型收缩；2）这些收缩的调节机制；3）哪些受体和细胞内信号分子可以作为靶点来刺激特定类型的收缩以加速或延缓运输；4）动物模型和实验方法在筛选潜在促动力药物对功能性肠道疾病患者肠道推进功效方面的优势和局限性。
