REDUCTION OF NEUROMUSCULAR BLOCKING ACTIVITY OF QUATERNARY COMPOUNDS BY GANGLIOSIDES

¹ National Institute of Neurological Diseases and Blindness, National Institutes of Health, U. S. Department of Health, Education, and Welfare, Bethesda, Maryland

Gangliosides isolated from beef brain reduce the neuromuscular blocking activity of d-tubocurarine and certain other diquaternary aromatic neuromuscular blocking agents. The activities of the nonaromatic diquaternary compounds, succinylcholine and decamethonium, were not influenced by gangliosides. The activity of a nonquaternary aromatic neuromuscular blocking compound, dihydro--erythroidine, also was unaffected.

The intact gangliosides appear to be necessary for activity since both asialogangliosides prepared by acid hydrolysis and some of the individual chemical components of the gangliosides did not change blocking activity.

The effect of the gangliosides also was observed when contact with the tissue receptors was prevented. The gangliosides had no influence on the activity of acetylcholine or carbamylcholine, substances which presumably act at the same tissue sites as the blocking compounds. The gangliosides are thus believed to prevent neuromuscular blockade by lowering the effective concentration of the blocking substances by an interaction between these compounds and ganglioside molecules or aggregates of molecules.