Acetylcholine, in the presence of
atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by
hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus
hexamethonium distinguishes between sympathetic nerve stimulation and the action of
acetylcholine. If
bretylium is used instead of
hexamethonium, there is no such distinction, for
bretylium blocks the response to nerve stimulation as well as that to
acetylcholine. It appeared that
hexamethonium might block the action of
acetylcholine by preventing its entry into the sympathetic fibre.
Acetylcholine has some structural similarity to
bretylium, since
acetylcholine is a derivative of trimethylammonium and
bretylium is a derivative of dimethylethylammonium. It has been found that
hexamethonium,
pentolinium and
hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of
bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that
mecamylamine and
pempidine, which are
ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre.