Brain protection of nicergoline against hypoxia: EEG brain mapping and psychometry : ∗E. Paulus, B. Saletu, J. Grünberger, L. Linzmayer and P. Anderer. Department of Pharmacopsychiatry, Psychiatric University Clinic of Vienna, Austria

Abstract

In a double-blind, placebo-controlled study the effect-kinetics on brain protection of a new retard formulation of codergocrine-mesylate (CDM) (Aramexe retard®, 5 mg) were investigated and compared with a standard CDM drug (5 mg Hydergine®) utilizing blood gas analysis, EEG mapping and psychometry. A transient, reversible hypoxic hypoxidosis (i.e. impairment of cerebral metabolism due to hypoxia) was experimentally induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2% nitrogen (N2) (found at an altitude of 6000 m), which was inhaled for 23 min under normobaric conditions by 18 healthy volunteers. After an adaptation session they received randomized 5 mg Aramexe retard, 5 mg Hydergine and placebo. Evaluation of blood gases, EEG mapping and psychometry was carried out at 0,2, 4,6, and 8 h after oral drug administration — each time under normoxic and hypoxic conditions. Blood gas analysis demonstrated a drop in SaO2 from 99% under normoxia to 70% under hypoxia, in Po2 from 100 to 33 mmHg, and in Pco2 from 36 to 31 mmHg, while pH increased from 7.43 to 7.48. Base excess and standard bicarbonate remained stable. Under hypoxia EEG mapping exhibited an increase in δ/θ, a decrease of α and increase of β activity, as well as a slowing of the centroid of the total power spectrum, which reflects deterioration of vigilance. Both CDM preparations significantly attenuated this vigilance decrement, with 5 mg Hydergine showing its encephalotropic peak effect in the second hour, 5 mg Aramexe retard in the sixth and eighth hours. At the behavioral level, hypoxic hypoxidosis induced a deterioration of the noo- and thymopsyche (by 53% under placebo), which was significantly mitigated by both 5 mg Aramexe retard (19%) and Hydergine (32%).