Metoclopramide on rat phrenic hemidiaphragm

The effect of metoclopramide on skeletal muscle and its neurotransmission was studied employing innervated and denervated rat diaphragm. Metoclopramide, at concentrations from 0.035 to 0.14 mM, inhibited the twitch contractions of rat diaphragm stimulated either directly or indirectly. Inhibition was greater in indirectly stimulated preparations, at a given concentration of metoclopramide, than in directly stimulated preparations. Inhibition of indirect twitch by metoclopramide could be intensified by raising the concentration of magnesium chloride, but was unaffected by physostigmine or d-tubocurarine. Metoclopramide also inhibited the submaximal contractures of denervated diaphragm elicited by potassium chloride and acetylcholine. In calcium-free physiological solution, metoclopramide inhibited the caffeine-induced contractures of denervated diaphragm as a function of its concentration. It is suggested that metoclopramide possesses a calcium antagonistic action in the rat diaphragm.