Effect-kinetics on brain protection of two codergocrine-mesylate preparations (Aramexe retard® and Hydergine®) by EEG mapping and psychometry under hypoxia

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 (O 2) and 90.2% nitrogen (N 2) (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 SaO 2 from 99% under normoxia to 70% under hypoxia, in P o 2 from 100 to 33 mmHg, and in P co 2 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%).