The butyrophenone neuroleptic haloperidol (10.65-85.2 microM) blocked the indirectly elicited twitch response of rat phrenic nerve diaphragm preparation. The depression was poorly reversible and was not mediated through dopamine receptors since neither dopamine nor apomorphine could alter the haloperidol blockade. Experiments on the isolated phrenic nerve indicated that the excitability of the nerve was blocked by haloperidol (42.6 microM) and that this blocking effect was minimized in presence of a high concentration of Ca2+ (5 mM) in the bathing fluid. Haloperidol (10.65-85.2 microM) also concentration-dependently inhibited acetylcholine (2.7 microM) contracture, without affecting the potassium chloride (0.5 M) and caffeine (15 mM) contracture. We conclude that haloperidol acts as a local anaesthetic on the motor nerve, probably by affecting calcium channels.

Acetylcholine↗

PubMedDate not supplied

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.

Acetylcholine↗