N‐mythelated derivatives of barbituric acid, hydantoin and oxazolidinedione used in the treatment of epilepsy

Abstract

At the present time, derivatives of the 3 related heterocyclic structures, barbituric acid, hydantoin and 2,4-oxazolidinedione are commonly used for the treatment of epilepsy in human beings. The metabolic conversion to demethylated end products of the following derivatives was studied in man: mephobarbital (Mebaral) to phenobarbital; metharbital to barbital; Mesantoin to Nirvanol; trimethadione (Tridione) to 5,5-dimethyl-2,4-oxazolidinedione; and paramethadione (Paradione) to 5-ethyl-5-methyl-2,4-oxazolidinedione. When the methylated drugs are administered in a divided daily dosage schedule, the products of demethylation accumulate in the body in amounts much greater than when the parent compound is administered. The relation of the demethylated products to therapeutic and toxic effects is discussed.