THE GANGLION BLOCKING ACTION OF PROCAINAMIDE.
In cats and rabbits procainamide (20 to 50 mg, intravenously) produced a fall of blood pressure of 20 to 50 mm Hg which reached a maximal effect within 1 min and lasted for about 5 min. Procainamide reduced the pressor responses to nicotine and to carotid arterial occlusion and reduced the depressor response to vagal stimulation, but did not antagonize the actions of adrenaline or noradrenaline on blood vessels. The contractions of the nictitating membrane to stimulation of the preganglionic cervical sympathetic nerve were partially or completely blocked by 20 to 50 mg of procainamide given intravenously. The ganglion blocking effect was more abrupt in onset and more slow to recover than that due to hexamethonium and had about 1/250th of the activity of the latter. Procainamide (1 mg) reduced the acetylcholine output of the perfused superior cervical ganglion to below 30% of the control value and blocked transmission completely. Small doses (10 mug) reduced the acetylcholine output but hardly affected ganglionic transmission. Procainamide, injected into the perfused superior cervical ganglion, blocked contractions elicited by stimulation of the preganglionic cervical sympathetic nerve for a longer period than those produced by acetylcholine injected into the perfusion circuit to the ganglion; the reverse was true for hexamethonium. Procainamide reduced the size of action potentials recorded from the superior cervical ganglion without altering the resting potential of the ganglion. The ganglion blocking activities of procainamide and hexamethonium often potentiated each other, especially when the preparation had been set up for several hours. On the guinea-pig isolated ileum preparation, procainamide (0.5x10(-4) g/ml.) antagonized responses due to acetylcholine, histamine and, most effectively, to nicotine. On the isolated heart, procainamide (1 mg) almost abolished the bradycardia produced by acetylcholine; 10 mg slowed and weakened the heart, while 100 mg stopped it. We conclude that procainamide, like procaine, blocks ganglionic transmission by (1) depressing the release of acetylcholine from preganglionic nerve endings; and (2) competing, with the acetylcholine which is released, for receptor sites on the ganglion cells. The amounts required to produce significant effects in vivo and in vitro are comparable. The methods available for detecting this type of ganglion blocking action are discussed.