title: On brain protection of co-dergocrine mesylate (Hydergine) against hypoxic hypoxidosis of different severity: double-blind placebo-controlled quantitative EEG and psychometric studies.
abstract: Utilizing quantitative EEG and psychometric methods we investigated in two subsequent double-blind, placebo-controlled trials the following questions: 1) Does co-dergocrine mesylate (CDM) protect against cerebral hypoxic hypoxidosis as objectivated by neurophysiological and behavioral measures in man? 2) Does CDM offer protection equally both against moderate and marked hypoxia induced experimentally by inhalation of a gas mixture of 9.8% and 8.6% O2 (equivalent to 6000 m and 7000 m altitude, respectively)? 3) Are brain-protective effects of CDM improving by drug administration over a longer period of time (2 weeks)? In the first study, hypoxic hypoxidosis was induced by a fixed gas combination of 9.8% oxygen and 90.2% N2 (equivalent to 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 15 healthy volunteers. They received randomized after an adaptation session placebo and 5 mg CDM. Blood gases, quantitative EEG, and psychometric measures were obtained under normoxic (21% O2) and hypoxic (9.8% O2) conditions before as well as 2, 4, 6 and 8 h after oral drug administration. Blood gas analysis demonstrated under hypoxia a drop in PO2 from 91 to 37 mmHg and in PCO2 from 38 to 33 mmHg, while pH increased from 7.41 to 7.47. Computer-assisted spectral analysis of the EEG showed an increase of delta/theta, decrease of alpha, and an increase of superimposed fast beta activity indicative of deterioration in vigilance. The latter was documented at the behavioral level by deterioration of intellectual and mnestic functions, psychomotor activity, performance in a reaction time task, mood, and wakefulness. CDM attenuated significantly this brain dysfunction, as it attenuated delta/theta and increased alpha-adjacent beta activity. Psychometric performance based on all 11 variables deteriorated under hypoxia by 49% after placebo, while after 5 mg CDM only by 26%. However, in a subsequent double-blind placebo-controlled trial in 12 healthy young volunteers, further augmentation of hypoxia induced by inhalation of a gas combination of 8.6% O2 and 91.4% N2 (equivalent to 7000 m altitude) leading to a drop of PO2 and PCO2 to 32 and 32 mmHg, respectively and an increase of pH to 7.46 resulted in a loss of brain protection, even when CDM was given over 2 weeks daily. Our findings suggest that treatment of organic brain syndromes with nootropic/antihypoxidotics should be initiated in an early rather than a late stage.
authors.affiliation: Division of Pharmacopsychiatry, Psychiatric University Clinic of Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Saletu
authors.forename: J
authors.initials: J
authors.lastname: Grünberger
authors.forename: R
authors.initials: R
authors.lastname: Anderer
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001519:Behavior / Q000187:drug effects / Q000502:physiology; D001784:Blood Gas Analysis; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004088:Dihydroergotoxine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology; D011594:Psychometrics
chemical_list: D004088:Dihydroergotoxine; D010100:Oxygen