Editing Phenytoin (section)

==History==
Phenytoin (diphenylhydantoin) was first synthesized by German chemist [[Heinrich Biltz]] in 1908.<ref name=Biltz>{{ cite journal | vauthors = Biltz H | journal = Chemische Berichte |trans-title=Constitution of the Products of the Interaction of Substituted Carbamides on Benzil and Certain New Methods for the Preparation of 5,5-Diphenylhydantoin | title = Über die Konstitution der Einwirkungsprodukte von substituierten Harnstoffen auf Benzil und über einige neue Methoden zur Darstellung der 5,5-Diphenyl-hydantoine | language = de | year = 1908 | volume  = 41 | issue = 1 | pages = 1379–1393 | doi = 10.1002/cber.190804101255 | url = https://zenodo.org/record/1426279 }}</ref>
Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, other physicians, including [[H. Houston Merritt]] and [[Tracy Putnam]], discovered phenytoin's usefulness for controlling seizures, without the sedative effects associated with [[phenobarbital]].<ref>{{cite journal | vauthors = Friedlander WJ | title = Putnam, Merritt, and the discovery of Dilantin | journal = Epilepsia | volume = 27 | issue = Suppl 3 | pages = S1-20 | date = 1986 | pmid = 3527690 | doi = 10.1111/j.1528-1157.1986.tb05743.x | s2cid = 7761284 }}</ref>

According to ''Goodman and Gilman's Pharmacological Basis of Therapeutics'':

<blockquote>In contrast to the earlier accidental discovery of the antiseizure properties of [[potassium bromide]] and phenobarbital, phenytoin was the product of a search among nonsedative structural relatives of phenobarbital for agents capable of suppressing electroshock convulsions in laboratory animals.<ref>{{ cite book | title = Goodman and Gilman's Pharmacological Basis of Therapeutics | edition = 10th | location = New York | publisher = McGraw-Hill | year = 2001 }}</ref></blockquote>

It was approved by the FDA in 1953 for use in seizures.{{cn|date=January 2025}}

[[Jack Dreyfus]], founder of the [[Dreyfus Fund]], became a major proponent of phenytoin as a means to control nervousness and [[clinical depression|depression]] when he received a prescription for Dilantin in 1966. He has claimed to have supplied large amounts of the drug to [[Richard Nixon]] throughout the late 1960s and early 1970s, although this is disputed by former White House aides<ref>{{cite news | vauthors = Stout D |date=31 August 2000 |title=2 Nixon Aides Skeptical About Report That He Took Drug |url=https://www.nytimes.com/2000/08/31/us/2-nixon-aides-skeptical-about-report-that-he-took-drug.html |work=[[The New York Times]] |access-date=6 February 2020}}</ref> and Presidential historians.<ref>{{cite web |title=New Nixon Biography Gives Salacious Details | vauthors = Campbell J |date=6 January 2006 |access-date=7 August 2021 |url=https://abcnews.go.com/Politics/story?id=123021 |website=[[ABC News (United States)|ABC News]] |publication-place=[[New York City]], [[New York (state)|New York]], United States of America | veditors = Muir D |editor1-link=David Muir |publisher=[[American Broadcasting Company]] ([[Walt Disney Television]]) }}</ref>
Dreyfus' experience with phenytoin is outlined in his book, ''A Remarkable Medicine Has Been Overlooked''.<ref>{{cite book | author = Dreyfus J | title = A Remarkable Medicine Has Been Overlooked: Including an Autobiography and the Clinical Section of the Broad Range of Use of Phenytoin | publisher = Continuum International Publishing Group | year = 1998 | isbn = 978-0-8264-1069-6 | url-access = registration | url = https://archive.org/details/remarkablemedic000drey }}</ref> Despite more than $70&nbsp;million in personal financing, his push to see phenytoin evaluated for alternative uses has had little lasting effect on the medical community.  This was partially because [[Parke-Davis]] was reluctant to invest in a drug nearing the end of its patent life, and partially due to mixed results from various studies.{{cn|date=January 2025}}

In 2008, the drug was put on the FDA's Potential Signals of Serious Risks List to be further evaluated for approval. The list identifies medications with which the FDA has identified potential safety issues, but has not yet identified a causal relationship between the drug and the listed risk. To address this concern, the Warnings and Precautions section of the labeling for Dilantin injection was updated to include additional information about [[Purple glove syndrome]] in November 2011.<ref>{{cite web|title=AERS data|url=https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm085914.htm|publisher=FDA|access-date=18 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140419025736/https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm085914.htm|archive-date=19 April 2014}}</ref>