Proof of antihypoxidotic properties of tenilsetam in man by EEG and psychometric analyses under an experimental hypoxic hypoxidosis

Abstract

AbstractProof of the protective properties against cerebral hypoxic hypoxidosis of a new potentially nootropic drug, tenilsetam (TEN), were studied as compared with 5 mg co‐dergocrine mesylate (CDM) in a double‐blnd, placebo‐controlled trial. Hypoxic hypoxidosis was induced by a fixed gas combination of 9.8% oxygen and 90.2% N2, equivalent to 6,000 m altitude, which was inhaled for 23 min under normobaric conditions by 15 healthy volunteers. They received randomized after an adapation session placebo, 150 mg, 300 mg, and 900 mg TEN 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 hr after oral drug administration. Blood gas analysis demonstrated under hypoxia a drop in PO2 from 91 to 37 mm Hg and in PCO2 from 38 to 33 mm Hg, while pH increased from 7.41 to 7.47. Under these hypoxic conditions, computer‐assisted spectral analysis of the EEG showed an increase of delta/theta, decrease of alpha, and 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. Both TEN and CDM attenuated this brain dysfunction, although in a different manner. Whereas TEN induced an increase in alpha and decrease of fast beta activity as compared with placebo, 5 mg CDM attenuated delta/theta and increased alpha‐adjacent beta activity. Multivariate analysis based on changes in all EEG‐variables exhibited the highest dosage TEN and the reference substance significantly different from placebo. Psychometric data added—despite high variance—further evidence for antihypoxidotic/nootropic properties of both drugs, as psychometric performance under hypoxia deteriorated by 45% after placebo, while after 5 mg CDM, 150 mg, 300 mg, and 900 mg TEN only by 25, 27, 39, and 22%, respectively. Based on changes in all 12 psychometric variables obtained at all times, 900 mg, but also 150 mg TEN as well as 5 mg CDM, were significantly different from placebo. Under normoxic conditions, multivariate analyses did not show any significant differences to placebo, and only singular neurophysiological and behavioral changes were observed.