PHARMACOLOGICAL ACTIONS OF OXAMIDES AND HYDROXYANILINIUM COMPOUNDS AT FROG NEUROMYAL JUNCTION

¹ Department of Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University, Chicago, Illinois

Oxamides (ambenonium, methoxyambenonium and their congeners) and two hydroxyanilinium compounds were studied on the frog nervesartorius preparations.

The two hydroxyaniliniums augmented, at relatively high concentrations, muscle twitch response to maximal indirect stimulation; among oxamides, only ambenonium produced similar effect. Both groups of compounds antagonized d-tubocurarine (d-Tbc) block.

Oxamides showed biphasic properties, blocking muscle twitch at higher concentrations.

Methoxyambenonium and two other oxamides, as well as hydroxyanilinium compounds augmented, without prolonging, the endplate potential (e.p.p.) and acetylcholine depolarization of the e.p. Ambenonium somewhat, and physostigmine and neostigmine markedly, augmented as well as prolonged the e.p. phenomena.

Hydroxyanilinium compounds, particularly 3-hydroxyphenyltriethyl ammonium, converted antidromic motor nerve spike into a repetitive response, and at higher concentrations, produced repetitive firing in nonstimulated nerve. These effects occurred at concentrations many times higher than those required to produce e.p. effects.

These findings are discussed from the viewpoint of the mechanism of facilitatory action of oxamides and of hydroxyaniliniums. Multiplicity of their neuromyal action, which includes post- and presynaptic phenomena, was stressed. It was suggested that postsynaptic events are of particular importance in anti-d-Tbc action of these compounds, and that, besides cholinesterase inhibition, a sensitizing mechanism of action at the e.p. is possible.