Discovery of phenytoin

Numerous letters and reports located in the Parke, Davis and Smithsonian files add to the story of Merritt's and Putnam's discovery of the anticonvulsant (AC) properties of phenytoin. The major events preceding this work were the fortuitous discovery of phenobarbital as an AC agent, structure/hypnotic activity studies with barbiturates and hydantoins in the early 1920s by A. W. Dox in the Parke, Davis laboratories, and the development of AC assay techniques in animals, by a number of laboratories. Phenytoin was the first item on the list of compounds sent to Putnam by Dox and W. G. Bywater in April 1936. It was found to have AC properties in animals late in 1936, but no public reports were issued until the following year. Clinical efficacy was established in 1937, but no public reports were issued until 1938. Dilantin sodium capsules were prepared by Parke, Davis & Co. and were ready for marketing the same year.