MODE OF ACTION OF ANTAGONISTS TO CURARE

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

1. Neostigmine, physostigmine, TEPP, and four 3-hydroxyphenyltrialkylam-monium compounds have been quantitatively compared on the frog rectus abdominis muscle with regard to direct stimulation, potentiation of ACh, inhibition of ChE, and antagonism to curare.

2. Statistically significant positive correlation has been demonstrated between potentiation of ACh, inhibition of ChE from frog muscle and bovine erythrocytes, and antagonism to curare by all the compounds tested. No significant correlation was found between direct stimulation of the muscle and any other property of these anti-curare agents.

3. None of the compounds potentiated the response of the muscle to nicotine.

4. 3-Hydroxyphenylmethyldiethylammonium bromide was the most potent antagonist to curare of the phenolic quaternary ammonium compounds; while 3-hydroxyphenyltrimethylammonium bromide was the most potent stimulator of the muscle.

5. It is postulated that the mode of action of the 3-hydroxyphenyltrialkylam-monium compounds, as antagonists to curare, is predominantly the result of their inhibitory effect on the cholinesterase present in the muscle.