Phenytoin - History

History

Phenytoin (diphenylhydantoin) was first synthesized by German chemist Heinrich Biltz in 1908. Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, outside scientists including H. Houston Merritt and Tracy Putnam discovered phenytoin's usefulness for controlling seizures, without the sedative effects associated with phenobarbital.

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

In contrast to the earlier accidental discovery of the antiseizure properties of 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.

There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Jack Dreyfus, founder of the Dreyfus Fund, became a major proponent of phenytoin as a means to control nervousness and depression when he received a prescription for Dilantin in 1966. He is believed to have supplied large amounts of the drug to Richard Nixon throughout the late 1960s and early 1970s. Dreyfus' experience with phenytoin is outlined in his book, A Remarkable Medicine Has Been Overlooked. Despite more than $70 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. It was approved by the USA Food and Drug Administration in 1953 for use in seizures.

Dilantin made an appearance in the 1962 novel One Flew Over the Cuckoo's Nest by Ken Kesey, both as an anticonvulsant and as a mechanism to control inmate behavior.

In 2008, the drug was put on the FDA's Potential Signals of Serious Risks List to be further evaluated for approval. The list means that the FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk.

According to the FDA's New Safety Information Identified by the Adverse Event Reporting System (AERS) Phenytoin Injection (Dilantin) has been associated with the risk of Purple Glove Syndrome.