Effects of some adrenergic neuron blockers, related quaternary ammonium compounds and guanidine derivatives on degenerating adrenergic nerves in the conscious rat.

Abstract

AbstractAdrenergic neuron blockers, related quarternary ammonium compounds and guanidine derivatives, and some other drugs have been tested on a degenerating nerve‐effector system in the rat periorbital smooth muscle. The main attention was paid to their influence on the degeneration contraction. The quaternary ammonium compounds structurally related to bretylium and xylocholine, with few exceptions, distinctly delayed the onset of the degeneration contraction. The guanidine derivatives known to be related to bretylium and xylocholine pharmacologically caused almost no delay. The simple compound phenyltrimethylammonium (PTMA) was chosen for further studies. It was found to possess actions on the degenerating system similar to those of bretylium. The PTMA‐induced delay was efficiently reduced by desmethylimipramine, but not at all by anticholinergic drugs.Conclusions: — Guanidine derivatives are much less efficient delayers than related quaternary ammonium compounds. The main structural features essential for delaying activity are found in PTMA. There does not seem to be any correlation between the neuron‐blocking or the sympathomimetic activity and the delaying effect of the drugs. The processes responsible for the onset of the normal degeneration contraction and those effecting the drug‐induced delay do not appear to involve any cholinergic sites.