Effects of the novel neuroprotective agent, riluzole, on human brain function and behavior: II. Double-blind, placebo-controlled EEG mapping and psychometric studies under hypoxia.
In a double-blind, placebo-controlled study, the antihypoxidotic properties of the novel neuroprotective agent, riluzole, were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. The latter was induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 20 healthy, young volunteers. They randomly received, after an adaptation session, single oral doses of placebo, and 50, 100 and 200 mg riluzole. Evaluation of blood gases, EEG mapping and psychometry 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 106 to 37 and 36 mmHg, in PCO2 from 35 to 31 and 31 mmHg at 14 and 23 min of inhalation, respectively, while pH increased from 7.43 to 7.48 and 7.48. Base excess and standard bicarbonate remained stable. EEG mapping exhibited under hypoxia a marked increase of delta/theta, decrease of alpha and an increase of superimposed beta activity, as well as a slowing of the centroid of the total activity, which reflects deterioration of vigilance. Riluzole in lower doses and at early hours after higher 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 power increased at 2-8 h after 50 mg riluzole and up to 4 h after 100 mg riluzole, while a decrease occurred at 4 and 8 h after 100 mg and at 6-8 h after 200 mg. Alpha power showed no 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 changes thereafter. Beta power decreased at various times after all three doses. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noopsyche, which was not mitigated by riluzole. In regard to the thymopsyche, there was even a slight deterioration after all three doses, as compared with placebo.
Saletu
B
B
Department of Pharmacopsychiatry and Sleep Research, University of Vienna, Austria.
Grünberger
J
J
Anderer
P
P
Linzmayer
L
L
D000328:Adult; D000339:Affect / Q000187:drug effects; D000531:Altitude; D000704:Analysis of Variance; D001784:Blood Gas Analysis; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D003700:Delta Rhythm / Q000187:drug effects; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D000860:Hypoxia; D008297:Male; D015999:Multivariate Analysis; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D011594:Psychometrics; D019782:Riluzole; D013826:Theta Rhythm / Q000187:drug effects; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D018696:Neuroprotective Agents; D013844:Thiazoles; D019782:Riluzole