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EEG mapping central effects of multiple doses of linopirine—a cognitive enhancer—in healthy elderly male subjects
Author(s) -
Saletu B.,
Darragh A.,
Breuel H. P.,
Herrmann W.,
Salmon P.,
Coen R.,
Anderer P.
Publication year - 1991
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.470060402
Subject(s) - morning , electroencephalography , placebo , medicine , vigilance (psychology) , psychology , dosing , anesthesia , audiology , neuroscience , alternative medicine , pathology
In a double‐blind, placebo‐controlled parallel group study, the encephalatropic effects of multiple doses of linopirine (DUP 996), a novel phenylindolinone derivative enhancing the stimulated release of acetylcholine in cholinergic nerve terminals, but also increasing concentrations of dopamine and serotonin, were investigated in 30 elderly, healthy volunteers. Fifteen subjects were randomly assigned to receive 20 mg DUP 996 b.i.d. and 15 were assigned to receive placebo. The doses were given at 12‐h intervals for 10 days with an additional morning dose on day 11. Multi‐lead EEG recordings were obtained after an adaptation session on day −1, as well as on days 2, 5 and 10 prior to and in the second hour after the morning dose. Computer‐assisted spectral analysis of the EEG and subsequent topographic brain mapping of the drug‐induced EEG changes demonstrated significant central effects of DUP 996, characterized by an augmentation of total power, decrease of delta and theta activity, increase in alpha and beta activity and an acceleration of the centroid. These findings are opposite to those seen in dementias and indicative of an improvement in vigilance, and have also been described with other cognition‐enhancing drugs. Time‐course investigations demonstrated more CNS changes 2 hours after than before morning oral dosing on days 2 and 5. The pharmacodynamic peak was observed in the 2nd hour after dosing on day 2. Topographically, the drug‐induced changes over time were most pronounced over fronto‐temporal, temporo‐occipital, parietal and frontal regions, e.g. over brain areas afflicted most by Alzheimer's disease.