It is a sodium channel blocker of cardiomyocytes; thus it is classified by the Vaughan Williams classification system as class Ia.

[3] For example, it can be used to convert new-onset atrial fibrillation, and although was initially thought to be suboptimal for this purpose, a growing body of literature is amounting in support for this exact cause.

There is also a chance that drug-induced lupus erythematosus occurs, which at the same time leads to arthralgia, myalgia and pleurisy.

[12] Many symptoms resemble systemic lupus erythematosus because procainamide reactivates hydroxylamine and nitroso metabolites, which bind to histone proteins and are toxic to lymphocytes.

The release of hydrogen peroxide is also called a respiratory burst, which occurs for procainamide in monocytes but not in lymphocytes.

This results in a disturbance in the artificial membrane potential and leads to a supraventricular tachycardia which induces failure of the pacemaker and death.

It induces rapid block of the batrachotoxin (BTX)-activated sodium channels of the heart muscle and acts as antagonist to long-gating closures.

Procainamide is present in charged form and probably requires a direct hydrophobic access to the binding site for blocking of the channel.

Due to its charged and hydrophilic form, procainamide has its effect from the internal side, where it causes blockage of voltage-dependent, open channels.

Procainamide slows the conduction velocity and increases the refractory period, such that the maximal rate of depolarization is reduced.

[25] Due to the loss of Indonesia in World War II, the source for cinchona alkaloids, a precursor of quinidine, was reduced.

[26] In 1936 it was found by Mautz that by applying it directly on the myocardium, the ventricular threshold for electrical stimulation was elevated.

However, due to the short duration of action, caused by rapid enzymatic hydrolysis, its therapeutic applications were limited.

It was found that procainamide was effective for treating ventricular arrhythmias, but it had the same toxicity profile as quinidine, and it could cause systemic lupus erythematosus-like syndrome.