Early clinical pharmacological trials with a new anti-epileptic, milacemide, using pharmaco-EEG and psychometry

In a double-blind placebo-controlled study the encephalotropic and psychotropic properties of milacemide (CP 1552 S) - a new derivative of glycine showing anti-convulsant action by increasing GABA concentrations and endogenous glycine pools in the brain - were studied in 12 normal subjects by means of quantitative EEG and psychometric analyses. They received randomized in weekly intervals single oral doses of 400 mg, 800 mg and 1600 mg milacemide, placebo as well as 600 mg sodium valproate and 1600 mg piracetam as reference compounds. EEG recordings and monitoring of blood pressure, heart rate and side effects were done at the hours, 0, 1, 2, 4, 6 and 8. Psychometric tests were performed at the hours 0, 2, 4, 6 and 8. Computer-assisted spectral analysis of the EEG showed significant effects of milacemide on the central nervous system (CNS) as compared with placebo, characterized by an attenuation of the delta activity as well as by an acceleration of the centroid of the slow activity but also of the total activity after all 3 doses. In addition, we noted an increase of beta activity after 400 mg, an increase of alpha activity after 800 mg, as well as an increase of alpha activity but decrease of beta activity after 1600 mg. These alterations, also seen after 600 mg sodium valproate, are reminiscent of quantitative EEG changes described after anti-epileptic drugs used in the treatment of Petit mal or generalized non-convulsive epilepsy. Moreover, they are also indicative of improvement in "vigilance" in the sense of Head which was also seen at the behavioural level specifically after the lowest doses of milacemide, as psychometric test demonstrated an improvement in attention, concentration, psychomotor activity and after-effect (indicating CNS-activation) as measured by means of the Archimedean spiral. This beneficial influence on performance declined with increasing doses. Evaluation of pulse, blood pressure and side effects demonstrated good tolerance after all administered substances. The findings are discussed.