Differential effects of metoclopramide and zetidoline on gastrointestinal motility.
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.
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C027277:zetidoline; D008787:Metoclopramide