Sanger G J
J Pharm Pharmacol. 1985 Sep;37(9):661-4. doi: 10.1111/j.2042-7158.1985.tb05108.x.
The experiments examine the actions of metoclopramide and domperidone on the responses evoked by electrical field stimulation or by acetylcholine, in longitudinal muscle strips obtained from human stomach. Electrical field stimulation evoked contractions which were predominantly cholinergically mediated; metoclopramide 0.28-28 microM caused a concentration-dependent increase in the height of these contractions. In the presence of atropine and barium chloride, electrical stimulation evoked relaxations of the stomach muscle, probably by stimulating non-adrenergic, non-cholinergic inhibitory nerves; metoclopramide 28 microM had no effect on these relaxations. Metoclopramide 0.003-2.8 microM had no effect on contractions evoked by exogenous acetylcholine, although higher concentrations of the drug increased the contractions. The results suggest that in human isolated stomach, low concentrations of metoclopramide may increase electrically evoked cholinergic activity by increasing the release of neuronal acetylcholine. Stimulation by metoclopramide of cholinergic activity in the gut may therefore be an important mechanism by which the drug increases gastrointestinal motility during therapy. Cholinergically mediated contractions were not increased by domperidone, and other mechanism(s) of action may therefore be important for this drug.
这些实验研究了甲氧氯普胺和多潘立酮对从人胃获取的纵行肌条中电场刺激或乙酰胆碱所诱发反应的作用。电场刺激诱发的收缩主要由胆碱能介导；0.28 - 28微摩尔的甲氧氯普胺使这些收缩的幅度呈浓度依赖性增加。在阿托品和氯化钡存在的情况下，电刺激诱发胃肌舒张，可能是通过刺激非肾上腺素能、非胆碱能抑制性神经；28微摩尔的甲氧氯普胺对这些舒张无影响。0.003 - 2.8微摩尔的甲氧氯普胺对外源性乙酰胆碱诱发的收缩无影响，尽管更高浓度的该药物会增加收缩。结果表明，在人离体胃中，低浓度的甲氧氯普胺可能通过增加神经元乙酰胆碱的释放来增强电诱发的胆碱能活性。因此，甲氧氯普胺对肠道胆碱能活性的刺激可能是该药物在治疗期间增加胃肠动力的重要机制。多潘立酮不会增加胆碱能介导的收缩，因此该药物可能存在其他重要的作用机制。
