A new drug for petit mal epilepsy

A NEW COMPOUND in the treatment of petit ma1 epilepsy, a-ethyl-a-methylsuccinimide, is the third evolving from our investigation into the treatment of this condition, and, like its predecessors Milontin (methylphenylsuccinimide) and Celontin ( N-methyl-a, a-methylphenylsuccinimide) it is also a member of the new succinimide chemical series. When this research was begun about ten years ago, only two compounds existed which could make any serious claims to effectiveness against petit ma1 attacks phenobarbital and trimethadione (Tridione) . Any other drug existing at that time had at best only a fringe effect on petit ma1 epilepsy. Phenobarbital has a limited, but broad spectrum, effect on grand mal, petit mal, and other types of epilepsy. It is probably for this reason that the drug persists as a mainstay in the armamentarium of many physicians today, in spite of its known obtunding effect on mentation. Tridione, on the other hand, has a brilliant and dramatic effect upon petit ma1 epilepsy, but its unpredictable, though rare, property of causing death from blood changes does not augur well for the peace of mind of the physician. Its other side effects like photophobia and rash are, like the side effects of other drugs, disconcerting, but bearable and not serious. The need for new and better drugs to treat petit ma1 epilepsy was great. Our therapeutic goal, naturally, was to evolve a compound equal or superior to Tridione, without its grave side effects. Put in another way, our aim was to avoid paying a high therapeutic price for a high therapeutic goal. This is a pharmacologic tight rope balancing feat since it is well known that toxicity frequently tends to increase with therapeutic effectiveness. The first drug evolved was, as is often the case, a therapeutic compromise in the interest of safety. Milontin had the virtues of complete safety and mild or innocuous side effects; the necessity of high dosage levels to achieve a good therapeutic effect, however, proved to be a disadvantage which, in turn, led to a secondary psychologic disadvantage. Most parents are impatient for an immediate therapeutic effect; the need to increase the dosage slowly up to the necessary effective level without the sudden, dramatic reduction in attacks elicited with Tridione often proved discouraging to parents and, probably, to the doctor himself at times. Further, people are quite prone to feel that the more medicine required, the more chance there is for a serious toxic reaction. This mental attitude acts as a deterrent to parental cooperation, vitally needed by the physician. In that respect, Milontin has stood the test of time in the mildness of its side effects and is therefore still the drug of choice. Celontin, the second drug evolved, grew out of our efforts to find a faster acting, but still not seriously toxic, medication. This drug, we feel, will become an invaluable addition to the therapeutic armamentarium in the treatment of epilepsy when its effectiveness is more generally known. Coincidentally, in contrast to Milontin, we found it had a broad spectrum of activity; it is the only drug we know that has a high degree of effectiveness against [ I ] psychomotor attacks, [2] petit ma1 attacks with a psychomotor element, and [3] the frequently seen mixed type of attack that defies proper classification. The therapeutic price, while greater than Milontin, is still not serious and has caused no blood dyscrasias in any of our patients over several years’ observation. A-ethyl-a-methylsuccinimide, hereafter designated by its laboratory number of PM 871, is the third compound and the subject of this