New antiepileptic drugs
Roger J. Porter, MD
National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
NEW medications are the best hope for tens of thousands of patients in the United States—and many more worldwide—for control of their epileptic seizures. Only a few patients whose disease is currently refractory to available medications can be considered for surgical intervention; other nonmedical therapies such as biofeedback appear to have a similarly limited role. This paper examines a few of the issues related to the development of new antiepileptic drugs (AEDs) and considers some of the data on the most important of these new compounds. Current therapy has been reviewed in detail elsewhere.1,2
EARLY ANTIEPILEPTIC DRUGS
In the nineteenth century, bromides were widely used as antiepileptic agents. In the United States, the modern history of AEDs begins in 1912 with the introduction of phenobarbital, a synthetic sedative-hypnotic drug which was shown to reduce seizure frequency (Table 1).3
As it proved to be more effective and less toxic than potassium bromide, phenobarbital soon became the drug of choice. Since the barbituric acid molecule is easily modified, many analogues of phenobarbital were synthesized, of which approximately 50 were marketed in the first 35 years of this century. One of these analogues, mephobarbital, demonstrated good antiepileptic activity and was marketed in the United States in 1935.4
In the absence of experimental models of seizures that could be used to test anticonvulsant activity, the discovery of the antiepileptic effect of bromide and phenobarbital was serendipitous. Later, with the development of seizure models, the search for new AEDs was based on scientific. . .