Allescher H D
II. Medizinische Klinik und Poliklinik TU München.
Z Gastroenterol. 1991 Apr;29 Suppl 3:27-30.
This article gives an overview on possible new pharmacological tools to modify gastrointestinal motility and/or secretion. The characterization of new subclasses of classical neurotransmitter receptors and of peptidergic receptors offer a new approach for the development of new therapeutic agents. Using molecular biology techniques a variety of receptor subclasses have been demonstrated for muscarinic and alpha 2-adrenergic receptors. Both receptor types are of major importance for the regulation of mucosal secretion in the submucosal plexus and specific ligands for these receptor subtypes could be of clinical interest. In the next paragraphs the possible therapeutic relevance of 5-HT3-receptor antagonists and of opiate agonist and -antagonists is discussed. 5-HT3-antagonists, which can be used as potent antiemetics, also demonstrate quite potent effects on upper gastrointestinal motility such as gastric emptying. Whereas the subclassification of opioids has so far no specific therapeutic consequences there is some evidence that casomorphin, a derivative of the casein of the milk, could be used as a possible antidiarhoic substance. The use of antagonist and agonists on peptidergic receptors with orally active ligands offer a further new therapeutic approach. This is discussed for CCK-antagonists and erythromycin-analogues which are agonists at the motilin receptor. Besides this experimental approach to modify defined receptor subclasses, there are new substances with so far not clearly defined mechanism of action, which, however, have potent therapeutic effects. Cisapride, a new potent prokinetic drug with little side effects, is now available for clinical use for a wide range of motility disorders.
本文概述了用于调节胃肠蠕动和/或分泌的可能的新药理学工具。经典神经递质受体和肽能受体新亚类的特性为新型治疗药物的开发提供了新方法。利用分子生物学技术,已证实毒蕈碱受体和α2-肾上腺素能受体存在多种受体亚类。这两种受体类型对黏膜下丛中黏膜分泌的调节都很重要,这些受体亚型的特异性配体可能具有临床意义。在接下来的段落中,将讨论5-HT3受体拮抗剂以及阿片类激动剂和拮抗剂可能的治疗相关性。5-HT3拮抗剂可作为强效止吐药,对诸如胃排空等上消化道蠕动也有相当强效的作用。虽然迄今为止阿片类药物的亚分类尚无特定的治疗结果,但有证据表明,酪蛋白(牛奶中的一种蛋白质)的衍生物酪蛋白吗啡可能用作一种潜在的止泻物质。使用具有口服活性配体的肽能受体拮抗剂和激动剂提供了另一种新的治疗方法。本文将对CCK拮抗剂和红霉素类似物(后者是胃动素受体激动剂)进行讨论。除了这种针对特定受体亚类进行调节的实验方法外,还有一些作用机制尚不明确但具有强效治疗作用的新物质。西沙必利是一种新型强效促动力药物,副作用小,现已可用于临床治疗多种动力障碍。