Pharmacological analysis of the effects of metoclopramide on the guinea pig isolated stomach.

A pharmacological analysis has been made of the effects of metoclopramide on the contractile activity of isolated longitudinal muscle strips prepared from the guinea pig stomach. Metoclopramide produced up to 3-fold increases in the amplitude of the spontaneous contractions exhibited by such a preparation. This phenomenon was antagonized by hyoscine but not by tetrodotoxin nor by hexamethonium. The contractile response to transmural stimulation was also enhanced by metoclopramide, as was the response to extrinsic acetylcholine. Neural inhibitory systems were not affected by metoclopramide. The apparent sensitization to extrinsic acetylcholine was, however, prevented by tetrodotoxin and hexamethonium, implying that this effect depends upon ganglionic stimulation by acetylcholine. These results suggest that metoclopramide may act by increasing the amount of acetylcholine released at the postgangionic cholinergic nerve ending.