The mode of neuromuscular blocking action of chlorpromazine.

The inhibitory action of chlorpromazine on skeletal muscle has been studied with isolated preparations. In the nerve-muscle preparations of the frog sartorius and the rat diaphragm, the twitch responses to indirect stimulation are much more strongly depressed by chlorpromazine than those to direct stimulation. The conductivity of the nerve trunk is unaffected. The contractures of the frog rectus abdominis muscle caused by acetylcholine are depressed by chlorpromazine,but the contractures due to KCl are not influenced. Larger doses of chlorpromazine cause contracture by themselves, and this cannot be prevented by tubocurarine. In the sartorius muscle of the toad, the depolarization due to acetylcholine is reduced by chlorpromazine. The paralysing action of chlorpromazine adds to that of tubocurarine, and is antagonized to some extent by eserine or neostigmine. Muscles treated with chlorpromazine do not completely recover on washing. High concentrations of chlorpromazine depress the release of acetylcholine by motor-nerve stimulation, although they do not affect the enzymic synthesis of acetylcholine by acetone-dried powder of guinea-pig brain. The differences between the neuromuscular block produced by chlorpromazine and that by tubocurarine are discussed.