Methoin in the Treatment of Epilepsy

Abstract

During the past ?\Q years several new anti-epileptic drugs have become available for clinical use: of these troxidone ( tridione ) is well known in the treatment of petit mal. This paper is a report on a trial of methoin ( mesontoin ; 3-methyl-5,5-phenylethyl hydantoin), a preparation mainly effective against other varieties of epilepsy. The drug is chemically allied to phenytoin, and is also related to the toxic drug phenylethylhydantoin ( nirvanol ) and to troxidone (Ruskin, 1948)?a fact of some significance when con sidering its toxic effects. It is dispensed as a pink tablet of 0.1 g. Clinical trials were first made in 1937 by Boiler (1943), who regarded it as valuable but potentially toxic. Results were first published in America in 1945, since when numerous reports upon its use have been made, though no detailed study has appeared in the literature of this country. Loscalzo (1945, 1946, 1947, 1948), using sodium diphenylhydantoinate ( dilantal ) in a four-year study, reported a 60% reduction of fits in patients suffering from major and minor epilepsy. Toxic effects were few, and the absence of gum hypertrophy and ataxia (com mon toxic symptoms with phenytoin) was notable. Kozol (1946, 1947, 1950), using doses of up to 1.8 g. a day, treated 200 patients for periods of up to four years, and found a 90% reduction in frequency of fits even though the majority of cases were resistant to phenytoin. Most of his cases suffered from major epilepsy, but the drug was also of use in psychomotor seizures, though not in petit mal. Methoin and phenytoin were sometimes given together, with apparently a synergistic effect ; pheno barbitone was not used, as methoin alone exerted a well-marked soporific effect. Harris and Otto (1947) treated 20 cases of psychomotor epilepsy and found that 13 were rendered attack-free. Fetterman and Weil (1947), Fetterman et al (1947), and Fetterman and Victoroff (1949), in a trial with 150 patients, considered methoin to be highly effective in major epilepsy, valu able in Jacksonian epilepsy, and of occasional use in psychomotor attacks. They stressed that good results were achieved when other remedies had failed. In petit mal the drug was not of use. Aird (1948) reported a group of 75 patients resistant to other measures, and found almost complete control in more than half the cases of major, psychomotor, and Jacksonian epilepsy. Although valuable, it soon became apparent that methoin was also sometimes toxic, and that its use called for the same careful supervision as with troxidone. Gibbs (1947) found that toxic reactions developed in 10% of patients, while of Lennox's (1946) cases 14% had a rash. Kozol (1947) reported a 6% incidence of morbilliform rashes during the first month of treatment, but thought that reactions were made less likely by the use of small initial doses. Loscalzo (1948) stated that a history of previous sensitization reactions was common in patients developing a rash, and stressed the need for a careful history in this respect. Drowsiness was commonly reported as a side-effect of methoin, but gum hypertrophy and ataxia, which so often occur during phenytoin treatment, were rarely seen.