ACTIONS OF HEMICHOLINIUM (HC-3) ON NEUROMUSCULAR TRANSMISSION.

Hemicholinium No. 3 (HC-3; alpha,alpha'-dimethylaminoethanol-4, 4'-biacetophenone) produced neuromuscular block of the tibialis anterior muscle-sciatic nerve preparation of the anaesthetized cat which was of slow onset, of long duration and dependent on the nerve stimulus frequency. The failure of the compound to modify the response of the tibialis muscle to close-arterial injections of acetylcholine suggested that the sensitivity of the motor endplate was not changed by it. The neuromuscular block produced by hemicholinium was antagonized by choline but only partly relieved by anticholinesterase drugs. The response to tetanic stimulation of the nerve during the neuromuscular block was well sustained and was followed by a slight posttetanic potentiation. The neuromuscular blocking action of hemicholinium could be relieved by temporary suspension of stimulation. These results suggest that the mode of action of hemicholinium at the neuromuscular junction is different from that of tubocurarine, and indicate that the action of hemicholinium is presynaptic, probably arising from a reduction in acetylcholine released by nerve stimulation.