Mechanisms of action of anti-seizure drugs and the anticonvulsant screening program of the National Institute of Neurological Disorders and Stroke.

OBJECTIVE To determine the efficacy of the Anticonvulsant Screening Program (ASP) of the National Institute of Neurological Disorders and Stroke (NINDS) in identifying new anti-seizure drugs with new mechanisms of action (MOA). The ASP does not itself identify the nature of the MOA, but on further basic investigation, many of these drugs prove eventually to have a wide variety of new and novel MOA. METHODS Data were tabulated from multiple sources, including the ASP and the literature. RESULTS Since it was established in 1975, the ASP has contributed to the identification of at least 9 new anti-seizure drugs. The effectiveness of the program was evaluated by ascertaining the number of MOA of the anti-seizure drugs discovered by the ASP screening techniques. Considering the MOA of drugs marketed after 1975 - and the MOA of investigational compounds not yet marketed - the ASP has contributed to the identification of anti-seizure drugs that possess 16 distinctly different MOA. CONCLUSION The ever-evolving screening approach of the ASP has many characteristics of a final common pathway for anti-seizure drug discovery.