Editing Procainamide (section)

==History==
Procainamide was approved by the US FDA on June 2, 1950, under the brand name "Pronestyl".<ref name=dafda>{{cite web |author= US Food and Drug Administration |author-link= US Food and Drug Administration |title= Drugs at FDA: FDA Approved Drug Products |url= https://www.accessdata.fda.gov/scripts/cder/daf/ |publisher= [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) |location= USA |access-date= 2012-08-13}}</ref> It was launched by [[Bristol-Myers Squibb]] in 1951.<ref name="pmid18610401">{{cite journal | vauthors = Hollman A | title = Procaine and procainamide | journal = British Heart Journal | volume = 67 | issue = 2 | pages = 143 | date = February 1992 | pmid = 18610401 | pmc = 1024743 | doi = 10.1136/hrt.67.2.143 }}</ref>
Due to the [[Japanese occupation of the Dutch East Indies|loss of Indonesia]] in [[World War II]], the source for [[cinchona alkaloids]], a precursor of [[quinidine]], was reduced. This led to research for a new [[antiarrhythmic drug]]. As a result, [[procaine]] was discovered, which has similar cardiac effects as quinidine.<ref name="one">{{cite journal | vauthors = Walker MJ | title = Antiarrhythmic drug research | journal = British Journal of Pharmacology | volume = 147 | issue = Suppl 1 | pages = S222–S231 | date = January 2006 | pmid = 16402108 | pmc = 1760742 | doi = 10.1038/sj.bjp.0706500 }}</ref> In 1936 it was found by Mautz that by applying it directly on the [[myocardium]], the ventricular threshold for electrical stimulation was elevated.<ref name="pmid18610401"/> This mechanism is responsible for the antiarrhythmic effect. However, due to the short duration of action, caused by rapid enzymatic hydrolysis, its therapeutic applications were limited.<ref name="three">{{cite book | vauthors = Moe GK, Abildskov A |chapter=Antiarrhythmic drugs | veditors = Goodman LS, Gilman A |title=Goodman and Gilman's The Pharmacological Basis of Therapeutics |edition=3rd |location=New York |publisher=Macmillan |year=1965 |pages=699–715}}</ref> In addition, procaine also caused tremors and [[respiratory depression]].<ref name="three" /><ref name="two">{{cite book |chapter=Historical development of antiarrhythmic drug therapy | veditors = Lüderitz BB |title=History of Disorders of Cardiac Rhythm |edition=3rd |location=New York |publisher=Wiley-Blackwell |year=2002 |pages=87–114}}</ref> All these adverse features stimulated the search for an alternative to procaine. Studies were done on various congeners and metabolites and this ultimately led to the discovery of procainamide by Mark ''et al''. 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.<ref name="one" /><ref name="two" /> These negative characteristics slowed the search for new antiarrhythmics based on the chemical structure of procainamide. In 1970 only five drugs were reported. These were the [[cardiac glycosides]], [[quinidine]], [[propranolol]], [[lidocaine]] and [[diphenylhydantoin]]. In January 1996, extended release procainamide hydrochloride (Procanbid extended-release tablets) was approved by the FDA.<ref>{{cite web |vauthors = Mishina E, Marroum P |year=2002 |url= https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/20545s007_Procanbid_biopharmr.pdf |archive-url= https://web.archive.org/web/20170218125158/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/20545s007_Procanbid_biopharmr.pdf |url-status= dead |archive-date= February 18, 2017 |title=Center for Drug Evaluation and Research Approval Package For: Application Number NDA 20-545/S007 |work=Clinical Pharmacology and Bioharmaceutics Review}}</ref>