GANGLIONIC STIMULATING PROPERTIES OF ALIPHATIC ESTERS OF CHOLINE AND THIOCHOLINE

¹ Department of Pharmacology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

The direct excitatory action of choline, two choline esters, and three thiocholine esters on the superior cervical ganglion of cats were compared with those of acetyleholine(ACh). When determined by the relative abilities of the choline esters to evoke postganglionic firing and ganglionic depolarizations that were blocked by hexamethonium (C6), ACh approximately 2 times more potent than propionyl- and butyrylcholine. The thiocholine esters, acetylthiocholine, butyrylthiocholine and acetyl--methylthiocholine, were considerably more potent than was ACh. While choline produced prominent postganglionic firing in does that were 3 to 4 times greater than ACh, the depolarization evoked by the same doses of choline was of low amplitude.

In contrast to the firing evoked by ACh, conditioning of the ganglia by repetitive preganglionic stimulation, anticholinesterase agents, or isoproterenol unmasked a lateoccurring atropine-sensitive component in the postganglionic responses to choline and the two choline esters only when large doses of the ganglionic stimulating drugs were employed. The above conditioning procedures failed to unmask atropine-sensitive firing in the postganglionic response to the thiocholine esters.

After pregaglionic stimulation, the postganglionic responses to thiocholine compounds were enhanced markedly and the depolarization produced by the compounds depressed. Small doses of atropine had no effect on the postganglionic discharges but partially reversed the depression of depolarization. In ganglia treated with an irreversible anticholinesterase agent, both the postganglionic firing and the ganglionic depolarization produced by the thiocholine esters were depressed. However, the postganglionic response to the compounds returned to control values within 30 to 40 minutes. The depression of the depolarization persisted for the duration of the experiments. Small doses of atropine antagonized the depression of depolarization but had no effect on the altered postganglionie responses to the thiocholine esters.

These findings are discussed against the background of multiple ganglionio cholinoceptive sites.