Buchheit K H, Buhl T
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Eur J Pharmacol. 1991 Nov 26;205(2):203-8. doi: 10.1016/0014-2999(91)90821-7.
Substituted benzamides such as metoclopramide, cisapride, zacopride, renzapride or BRL 20627, stimulate intestinal motility in various species. As they are antagonists at 5-HT3 and agonists at 5-HT4 receptors and as both mechanisms could potentially contribute to their gastrointestinal prokinetic effect, the underlying mechanism is unclear. To clarify this, the effect of some substituted benzamides on gut motility was investigated in the isolated guinea pig ileum using the Trendelenburg technique, in which pressure-induced peristaltic contractions are measured. All benzamides stimulated the peristaltic reflex with the rank order of potency: renzapride greater than cisapride greater than BRL 20627 greater than (+/-)-zacopride greater than metoclopramide. ICS 205-930, granisetron and 2-methyl-5-HT did not change the peristaltic response. 5-HT and 5-methoxytryptamine potently mimicked the effect of the benzamides. The effect of 5-HT was not blocked by ICS 205-930 (10(-7) M). These results indicate that the Trendelenburg preparation is suitable for the investigation of intestinal prokinetic effects of the substituted benzamides. Furthermore, the results suggest that the intestinal effect of benzamides results from activation of 5-HT4 receptors rather than from blockade of 5-HT3 receptors.
诸如甲氧氯普胺、西沙必利、扎考必利、瑞扎必利或BRL 20627等取代苯甲酰胺可刺激多种动物的肠道蠕动。由于它们是5-HT3受体拮抗剂和5-HT4受体激动剂，且这两种机制都可能对其胃肠道促动力作用有贡献，因此其潜在机制尚不清楚。为了阐明这一点，使用特伦德伦伯卧位技术，在离体豚鼠回肠中研究了一些取代苯甲酰胺对肠道蠕动的影响，该技术可测量压力诱导的蠕动收缩。所有苯甲酰胺均刺激蠕动反射，其效力顺序为：瑞扎必利＞西沙必利＞BRL 20627＞（±）-扎考必利＞甲氧氯普胺。ICS 205-930、格拉司琼和2-甲基-5-羟色胺未改变蠕动反应。5-羟色胺和5-甲氧基色胺能有效模拟苯甲酰胺的作用。5-羟色胺的作用未被ICS 205-930（10⁻⁷M）阻断。这些结果表明，特伦德伦伯卧位制备法适用于研究取代苯甲酰胺的肠道促动力作用。此外，结果表明苯甲酰胺的肠道作用是由5-HT4受体激活而非5-HT3受体阻断所致。
