The discovery of phenytoin did more than add another medicine. It helped create a systematic method for finding antiseizure drugs: screen compounds in reproducible seizure models and look for anticonvulsant activity separately from sedation.
The problem with accidental discovery
Potassium bromide and phenobarbital had reached epilepsy treatment partly through serendipity. By the 1930s H. Houston Merritt and Tracy Putnam wanted a deliberate experimental route to better medicines.
The maximal electroshock model
Merritt and Putnam used electrically induced seizures to test compounds for anticonvulsant activity. Their work identified phenytoin in the late 1930s as strongly antiseizure without the profound hypnotic effect of barbiturates.
Why the method was revolutionary
The scientific importance was larger than phenytoin itself. Antiseizure efficacy could now be screened experimentally rather than inferred from sedation. Later programmes used maximal electroshock and pentylenetetrazole models to identify different patterns of drug activity.
The Anticonvulsant Screening Program
In 1975 the US NINDS established the Anticonvulsant Screening Program, scaling standardised testing of candidate compounds and linking academic chemistry, animal models and clinical development.
From screening to modern discovery
Modern discovery now includes chronic epilepsy models, molecular targets, genetics and computational methods. Even so, the Merritt-Putnam approach remains a landmark in the move from serendipity to organised experimental science.
Related reading
Sources and further reading
- Development of antiepileptic drugs throughout history
- Brief history of anti-seizure drug development
- Epilepsy Therapy Screening From 1975 to 2026 and Beyond
Evidence checked: September 2026.