The effects of the triethyl analogue of
choline (triethyl 2-hydroxyethyl
ammonium) on muscular activity have been studied in conscious rabbits, chicks, dogs and a cat. The contractions of the tibialis anticus and soleus muscles of cats under
chloralose anaesthesia, and of the tibialis anticus muscle of rabbits under
urethane anaesthesia and the isolated diaphragm preparation of the rat were also used. In conscious animals,
triethylcholine caused a slowly developing
muscular weakness which was more severe after exercise and which resembled the symptoms of
myasthenia gravis. In nerve-muscle preparations
triethylcholine had a selective action in reducing the contractions of muscles elicited by a high rate of nerve stimulation while leaving unaffected the contractions caused by slower rates of stimulation. During the
paralysis of the tibialis muscle of the cat produced by
triethylcholine, action potentials recorded from the motor nerve were unaffected and the muscle responded normally to injected
acetylcholine and to direct electrical stimulation. The failure of neuromuscular transmission produced by
triethylcholine was reversed by injection of
choline, but
anticholinesterases were ineffective.
Choline reduced the toxicity of
triethylcholine in mice. It is concluded that
triethylcholine produces transmission failure at the neuromuscular junction by interfering with the ability of the nerve endings to synthesize
acetylcholine. The possibility that
triethylcholine is itself acetylated by the nerve endings and released as an inactive
neurohormone is discussed. It was shown that
triethylcholine was devoid of depolarizing action and
curare-like blocking action. It possesses a transient
ganglion blocking action of the
tetraethylammonium-type as shown in experiments in which it caused a fall in blood pressure and blocked the response of the nictitating membrane to pre- but not to post-ganglionic stimulation of the cervical sympathetic nerve.