EFFECT OF ANTIEPILEPTIC DRUGS ON THE ACETYLCHOLINE METABOLISM OF THE BRAIN

Abstract

SummaryA comparative study in vitro was made on the effect of some antiepileptic drugs upon the Ach metabolism in mouse's brain. The drugs employed for the experiment were 5 phenyl‐5‐ethyl‐barbituric acid (phecobarital) and 5.5‐diphenylhydavtoin (aleviatin), effective against grand mal type of epilepsy, and 3.5, Strimethyl‐oxazolidine ‐2.4‐dione (mkoaleviatin, an effectivum against petit mal type. The purpose was to contribute something elucidating for the mechanism of epilepsy biochemically. ChE activity was examined by the use of homogenate, and Ach sycthesis by the use of slices of brain tissue.The effect upon ChE activity was slightly inhibitory. A tendency reverse in nature was found between the effectiva against grand mal type and that against petit mal type. The result of the joint application of two kinds of drugs was approximately the same as that in the single application of the more effective drug, as far as the inhibitory aspect is concerned.As to the effect upon Ach synthesis, the anti‐grand mal type agents at low concentration rate returned always acceleration, at as high rate as 4 mM per liter, apparent inhibition of a ratio at 16% against the control rate; whereas anti‐petit mal type agent gave at low concentration rate again inhibition in a ratio of 70 60%, at 4 mM per liter 106% against the control case. At rates higher than that, inhibition became intensified, for instance of the maximum title, as high as 45% at 30mM per liter. Thereby, drugs inhered with acceleration at low concentration rate turned inhibitory by joint use of other agents.As the drugs with selective therapeutic effect each upon grand mal type resp. petit mal type proved to work quite different upon Ach metabolism of the brain, the biochemical aspect of epilepsy were discussed in the light of the newly established data, with a few problems for the future mentioned by the way.