The Presynaptic Effects of Quaternary Ammonium Compounds on the Acetylcholine Metabolism of a Sympathetic Ganglion

Many quaternary ammonium compounds owe their interference with cholinergic trans- mission to a blocking action at the postjunctional receptor.Studies at the ganglionic synapse (Paton & Perry, 1953) and neuromuscular junction (Bums & Paton, 1951) have given greater definition to this well-known facet of the pharmacological activity of quaternary bases; their anticholinesterase action is also well documented (see review by Long, 1963).Yet in contrast little is known of their prejunctional effects, especially at the secretory nerve terminals.With the introduction of the hemicholinium series by Long & Schueler in 1954 and subsequent investigations of the effects of the hemicholinium HC-3 (MacIntosh, Birks & Sastry, 1956; Birks & MacIntosh, 1961), it became clear that this quaternary base could interfere with the metabolism of acetylcholine -in cholinergic nerve terminals.There seemed no a priori reason to suppose such effects to be confined only to hemicholinium.Indirect evidence followed, suggesting that triethylcholine also affected acetylcholine turnover in much the same way as did hemicholinium (Bowman & Rand, 1961).The present paper describes the examination of various quaternary ammonium com- pounds, including the hemicholinium HC-3 and triethylcholine (triethyl-2-hydroxyethylammonium), upon presynaptic acetylcholine turnover, using the superior cervical ganglion of the cat.This ganglion, when isolated for perfusion, is particularly convenient for studying the functional acetylcholine metabolism of intact nerve endings because of its high density of cholinergic synapses (Brown & Feldberg, 1936b; MacIntosh, 1961).Preliminary reports of part of this work have been made