DIFFERENCES IN MODE OF NEUROMUSCULAR BLOCKADE IN A SERIES OF SYMMETRIC BIS-QUATERNARY AMMONIUM SALTS

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

The type of neuromuscular blockade caused by each of a series of symmetrical compounds containing two quaternary nitrogen atoms was investigated in the chicken sciatic nerve-gastrocnemius preparation and in mice. Mode of paralysis—tubocurarine-like (preventing muscle depolarization) or decamethonium-like (producing depolarization)—was influenced by 1) the distance between the quaternary nitrogen atoms, 2) the chemical structure of the chain between the nitrogen atoms, and 3) the number and structure of each of the chemical groups attached to the quaternary nitrogen atoms.

1. Of the members of the methonium series (from dimethonium through decamethonium) all but penta- and hexamethonium had a decamethonium-like action. Penta- and hexamethonium had actions similar to that of tubocurarine.

2. Independent of total chain length, replacement of methylene groups between nitrogen atoms by 2 cyclohexane groups produced an agent with a tubocurarine-like action; replacement of methylene groups by two phenyl groups preserved decamethonium-like activity. Introduction of two ether oxygen atoms into the polymethylene chain did not change the type of action, but changed the potency of the agents disproportionately to the change in total chain length.

3. Replacement of methyl groups on the quaternary nitrogen atoms by pyridine or pyrrolidine groups or an isopropyl group did not change the type of action of the agent. Replacement of methyl groups by ethyl, butyl, benzyl or nitrobenzyl groups produced agents with a tubocurarine-like action.

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