EFFECTS OF THE NOVEL NEUROPROTECTIVE AGENT, RILUZOLE, ON HUMAN BRAIN-FUNCTION AND BEHAVIOR .2. DOUBLE-BLIND, PLACEBO-CONTROLLED EEG MAPPINGAND PSYCHOMETRIC STUDIES UNDER HYPOXIA

In a double-blind, placebo-controlled study, the antihypoxidotic prope rties of the novel neuroprotective agent, riluzole, were investigated utilizing blood gas analysis, EEG mapping and psychometry under a tran sient, reversible, hypoxic hypoxidosis. The latter was induced by a fi xed gas combination of 9.8% oxygen (O-2) and 90.2% nitrogen (N-2) (fou nd at 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 20 healthy, young volunteers. They randomly received, af ter an adaptation session, single oral doses of placebo, and 50, 100 a nd 200 mg riluzole. Evaluation of blood gases, EEG mapping and psychom etry Were carried out 0, 2, 4, 6 and 8 h postdrug, each time under the 23-min hypoxia. Blood gas analysis demonstrated a drop in PO2 from 10 6 to 37 and 36 mmHg, in PCO2 from 35 to 31 and 31 mmHg at 14 and 23 mi n of inhalation, respectively, while pH increased from 7.43 to 7.48 an d 7.48. Base excess and standard bicarbonate remained stable. EEG mapp ing exhibited under hypoxia a marked increase of delta/theta, decrease of alpha and an increase of superimposed beta activity as well as a s lowing of the centroid of the total activity, which reflects deteriora tion of vigilance. Riluzole in lower doses and at early hours after hi gher doses did not attenuate this hypoxia-induced vigilance decrement, while with higher doses (100-200 mg) in later recording periods (6-8 h) brain protection occurred. As compared with placebo, delta/theta po wer increased at 2-8 h after 50 mg riluzole and up to 4 It after 100 m g riluzole, while a decrease occurred at 4 and 8 h after 100 mg and at 6-8 h after 200 mg. Alpha power changes after 50 mg, an increase at 2 and 8 h after 100 mg and a decrease at 4 h after 200 mg, with no chan ges thereafter. Beta power decreased at various times after all three poses. At the behavioral level, hypoxic hypoxidosis induced a deterior ation of the noopsyche, which was not mitigated by riluzole. In regard to the thymopsyche, there was even a slight deterioration after all t hree doses, as compared with placebo.