Effects of the novel neuroprotective agent, riluzole, on human brain function and behavior: I. Double-blind, placebo-controlled EEG mapping and psychometric studies under normoxia.
In a double-blind, placebo-controlled, crossover study, the encephalotropic and psychotropic properties of single oral doses of the novel neuroprotective agent, riluzole, were investigated utilizing EEG mapping and psychometry. Twenty healthy young volunteers received randomly at weekly intervals, placebo, 50, 100 and 200 mg riluzole. EEG recordings and evaluation of 9 noopsychic and 5 thymopsychic variables were carried out at 0, 2, 4, 6 and 8 h after oral drug administration. EEG maps on the multivariate analysis demonstrated that all three doses induced significant changes in human brain function, as compared with placebo, between 2 and 8 h, with effect only increasing slightly with dose. EEG maps on univariate analysis demonstrated generally an increase of delta/theta, decrease of alpha and beta power, as well as a slowing of the centroid of the total power spectrum, which suggests sedative properties of the drug. Only after the two highest doses at 6 h were some different findings observed. Multivariate statistics on psychometry failed to show any significant effects on the noopsyche, while for the thymopsyche, all three doses of riluzole produced a deterioration. The latter was characterized by a decrease in drive and wakefulness as well as deterioration in well-being, mood and affectivity. Thus, under normoxia, in all three doses riluzole produced neurophysiologically a sedative effect, accompanied at the behavioral level by a deterioration in the thymopsyche, which may be expected from a drug with antiglutamatergic effects in normals.