Adrenergic nerve-blocking activity of a new guanidine derivative.

The effects of 4-7-exo-methylene-hexahydroisoindoline-ethyl guanidine hemisulfate (no. 865-123) on norepinephrine release were investigated in the perfused spleen on the cat. No. 865-123 irreversibly blocked the release of norepinephrine evoked by nerve stimulation. Tetraethylammonium, 4-amino-pyridine and guanidine readily reversed this inhibitory effect, and the norepinephrine output was nearly tripled after repeated stimulation of the nerves. On subsequent perfusion with Krebs' solution without any drugs, the inhibitory effect of no. 865-123 partially reappeared. Perfusion pressure responses followed the same pattern as release except during the final perfusion period with Krebs' solution. It is suggested that tetraethylammonium, 4-aminopyridine and guanidine allow greater than normal amounts of calcium to accumulate inside the adrenergic nerve terminals during an action potential to reverse no. 865-123 blockade of norepinephrine release.