Editing Procainamide (section)

==Pharmacology==

===Mechanism of action===
Procainamide works as an [[anti-arrhythmic]] agent and is used to treat [[cardiac arrhythmia]]. It induces rapid block of the [[batrachotoxin|batrachotoxin (BTX)-activated]] [[sodium channels]] of the heart muscle and acts as antagonist to long-gating closures. The block is voltage-dependent and can occur from both sides; either from the intracellular or the extracellular side. Blocking from the extracellular side is weaker than from the intracellular side because it occurs via the [[hydrophobic pathway]]. Procainamide is present in charged form and probably requires a direct hydrophobic access to the binding site for blocking of the channel. Furthermore, blocking of the channel shows a decreased voltage sensitivity, which may result from the loss of voltage dependence of the blocking rate. Due to its charged and hydrophilic form, procainamide has its effect from the internal side, where it causes blockage of voltage-dependent, open channels. With increasing concentration of procainamide, the frequency of long blockage becomes less without the duration of blockage being affected. The rate of fast blocking is determined by the membrane depolarization. Membrane [[depolarization]] leads to increased blocking and decreased unblocking of the channels. Procainamide slows the conduction velocity and increases the [[Refractory period (physiology)|refractory period]], such that the maximal rate of depolarization is reduced.<ref name=Zamponi/> It is also said to be a [[binding selectivity|selective]] [[muscarinic acetylcholine receptor|muscarinic acetylcholine]] [[M3 receptor|M<sub>3</sub> receptor]] antagonist.<ref name="LavradorCabralVeríssimo2023">{{cite journal | vauthors = Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM | title = A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity | journal = Pharmaceutics | volume = 15 | issue = 1 | date = January 2023 | page = 230 | pmid = 36678858 | pmc = 9863833 | doi = 10.3390/pharmaceutics15010230 | doi-access = free | url = }}</ref>

===Metabolism===
Procainamide is metabolized via different pathways. The most common one is the [[acetylation]] of procainamide to the less-toxic [[N-acetylprocainamide]].<ref>{{cite journal | vauthors = Roden DM, Reele SB, Higgins SB, Wilkinson GR, Smith RF, Oates JA, Woosley RL | title = Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: comparison with procainamide | journal = The American Journal of Cardiology | volume = 46 | issue = 3 | pages = 463–468 | date = September 1980 | pmid = 6158263 | doi = 10.1016/0002-9149(80)90016-8 }}</ref> The rate of acetylation is genetically determined. There are two phenotypes that result from the acetylation process, namely the slow and rapid acetylator. Procainamide can also be oxidized by the [[cytochrome P-450]] to a reactive oxide metabolite. But it seems that acetylation of the nitrogen group of procainamide decrease the amount of the chemical that would be available for the oxidative route.<ref name="Uetrecht, J. P. 1981">{{cite journal | vauthors = Uetrecht JP, Freeman RW, Woosley RL | title = The implications of procainamide metabolism to its induction of lupus | journal = Arthritis and Rheumatism | volume = 24 | issue = 8 | pages = 994–1003 | date = August 1981 | pmid = 6169352 | doi = 10.1002/art.1780240803 }}</ref> Other metabolites of procainamide include desethyl-N-acetylprocainamide, desethylprocainamide, p-aminobenzoic acid, which are excreted via the urine.  N-acetyl-4-aminobenzoic acid as well as N-acetyl-3-hydroxyprocainamide, N-acetylprocainamide-N-oxide and N-acetyl-4-aminohippuric acid are also metabolites of procainamide.<ref name="Uetrecht, J. P. 1981"/>