Lobbezoo M W, Janszen F H, Tulp M T, Zwagemakers J M
Eur J Pharmacol. 1985 Jan 22;108(2):105-12. doi: 10.1016/0014-2999(85)90714-9.
There is a recently formulated hypothesis that metoclopramide (MCP) may stimulate gastrointestinal (GI) motility via an antagonistic action on presynaptic, release modulating muscarinic receptors. We have tested this hypothesis by comparing MCP and zetidoline (ZTD), another putative presynaptic muscarinic antagonist, in various GI motility assays. The muscarinic and dopamine receptor binding affinity was also measured. Both MCP and ZTD acted as stimulants of electrically induced twitches of the isolated guinea-pig ileum and as antagonists of the inhibitory effects of intermittent exposure to cholinomimetics on the same preparation. In vivo, MCP significantly accelerated GI transit in mice and gastric emptying in rats. In contrast, ZTD had no effect on these in vivo parameters. Thus MCP and ZTD seem to act on the isolated guinea-pig ileum as presynaptic muscarinic antagonists. However, this mechanism apparently does not contribute to stimulation of GI motility in vivo.
最近有一种假说认为，甲氧氯普胺（MCP）可能通过对突触前释放调节型毒蕈碱受体的拮抗作用来刺激胃肠（GI）蠕动。我们通过在各种胃肠蠕动试验中比较MCP和另一种假定的突触前毒蕈碱拮抗剂泽替多林（ZTD）来检验这一假说。还测定了毒蕈碱和多巴胺受体结合亲和力。MCP和ZTD均作为离体豚鼠回肠电诱发抽搐的刺激剂，以及作为间歇性暴露于拟胆碱药对同一制剂的抑制作用的拮抗剂。在体内，MCP显著加速小鼠的胃肠转运和大鼠的胃排空。相比之下，ZTD对这些体内参数没有影响。因此，MCP和ZTD在离体豚鼠回肠上似乎作为突触前毒蕈碱拮抗剂起作用。然而，这种机制显然对体内胃肠蠕动的刺激没有作用。
