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On the cerebro-protective effects of caroverine, a calcium-channel blocker and antiglutamatergic drug: Double-blind, placebo-controlled, EEG mapping and psychometric studies under hypoxia

Author(s): Grunberger, J., Anderer, P., Linzmayer, L., Konig, P.

Journal/Book: Br J Clin Pharmacol. 1996; 41: Osney Mead, Oxford, Oxon, England OX2 0EL. Blackwell Science Ltd. 89-99.

Abstract: 1 In a double-blind, placebo-controlled study, the acute antihypoxidotic properties of the calcium-channel blocking and antiglutamatergic caroverine were investigated utilizing blood gas analysis, EEG mapping and psychometry under a transient, reversible, hypoxic hypoxidosis. 2 The latter was induced by a fixed gas combination of 9.8% oxygen (O-2) and 90.2% nitrogen (N-2) (found in 6000 m altitude), which was inhaled for 23 min under normobaric conditions by 16 healthy, young volunteers. They received randomized after an adaptation session, single oral doses of placebo, 40, 80 and 120 mg caroverine. Evaluation of blood gases, EEG mapping and psychometry were carried out 0, 2, 4, 6 and 8 h post-drug, during hypoxia. 3 Blood gas analysis demonstrated a drop in Po-2 from 95 to 33 and 30 mmHg, in Pco(2) from 38 to 30 and 30 mmHg in the 14th and 23rd minute of inhalation, respectively, while pH increased from 7.41 to 7.50 and 7.51. Base excess and standard bicarbonate remained stable. 4 EEG mapping under hypoxia exhibited a marked increase of delta/theta, decrease of alpha and an increase of superimposed beta activity, which reflects deterioration of vigilance. 5 Caroverine attenuated this hypoxia-induced vigilance decrement in a dose- and time-dependent manner 6-8 h after 80 mg and 2-8 h after 120 mg. 6 Hypoxic hypoxidosis induced a deterioration of memory and attention variability, which was mitigated by 80 and 120 mg caroverine. However, there was an augmentation of the hypoxia-induced decrement in psychomotor performance after 120 mg. 7 The drug was well tolerated, and there were no significant differences compared with placebo with regard to pulse and blood pressure.

Note: Article B Saletu, Univ Vienna, Sch Med, Dept Psychiat, Wahringer Gurtel 18-20, A-1090 Vienna, Austria

Keyword(s): hypoxia; hypoxic hypoxidosis; caroverine; calcium-channel blocker; antiglutamatergic drug; EEG mapping; psychometry; memory; attention variability; fine motor activity; CO-DERGOCRINE MESYLATE; NON-NMDA RECEPTORS; BRAIN PROTECTION; NEURONAL INJURY; GLUTAMATE; NEUROPSYCHOPHARMACOLOGY

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