MODE OF ACTION OF ANTAGONISTS TO CURARE. II. ANTI-CURARE ACTION OF HYDROXYPHENYLTRIALKYLAMMONIUM COMPOUNDS IN AVIAN MUSCLE

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago 12, Illinois

The anti-curare activity of a series of phenyltrialkylammonium derivatives was investigated on the sciatic nerve gastrocnemius preparation of the anesthetized chicken.

1. Responses of the muscle to tubocurarine and decamethonium were studied. Tubocurarine produced a diminished amplitude of contraction; decamethonium produced both decreased amplitude of contraction and contracture of the, muscle.

2. Selectivity of action of anti-curare agents of the m-hydroxyphenyltrialkylammonium series seems to depend on the presence of the quaternary nitrogen atom in the molecule. Specificity of action seems dependent on substituents on the nitrogen atom, and on the phenyl ring.

3. It is suggested that the m-hydroxyphenyltrialkylammonium compounds exert their anti-curare action by virtue of their ability to inhibit cholinesterase:

a. When given alone in doses just effective in antagonizing tubocurarine, the compounds had effects qualitatively like those of tetraethylpyrophosphate (TEPP).

b. The agents antagonized the effects of tubocurarine in doses smaller than those required to produce contracture of the muscle.

c. Poor correlation existed between the potencies of the agents in antagonizing tubocurarme and their potencies in stimulating muscle contracture.

d. The presence of cholinesterase was essential to the anti-curare action of the m-hydroxyphenyltrialkylammonium compounds, since pretreatment of the animal with TEPP abolished the anti-curare activity of the agents without affecting their ability to cause contracture.