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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

EEG brain mapping in evaluating the time-course of the central action of DUP 996--a new acetylcholine releasing drug.

1. In a double-blind, placebo-controlled study the encephalotropic effects of DUP 996, a novel phenylindolinone derivative for Alzheimer's disease enhancing the release of acetylcholine in cholinergic nerve terminals in the brain only when its release is triggered, were studied with special consideration of the pharmacodynamic time-course. 2. Thirteen healthy male volunteers aged 18-40 years received randomized and at weekly intervals, single oral doses of placebo and 30 mg DUP 996. Blood sampling for plasma concentration analysis, EEG recordings and evaluation of pulse, blood pressure and side effects were carried out at 0, 1, 2, 4, 8, 12 and 24 h. 3. 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 suggesting vigilance-improving properties. The findings were characterized mostly by an augmentation of total power as well as by an increase of absolute power in the alpha and alpha-adjacent beta activity. 4. Time-course investigations demonstrated two pharmacodynamic peaks: a first one in the 2nd h and a second one in the 12th h. In detail CNS effects increased up to the 2nd h, showed a drop in the 4th h, increased again thereafter to peak in the 12th h. Even in the 24th h there were significant differences between DUP 996 and placebo. The latter suggests an indirect effect and/or an active metabolite, as the parent drug is rapidly absorbed and has a rather short plasma half-life between 1-3 h. 5. DUP 996-induced EEG-changes over time were most pronounced over temporo-occipital, temporo-frontal, parietal and frontal regions, e.g. over brain areas afflicted most by Alzheimer's disease. 6. Evaluation of vital signs, laboratory findings and ECG as well as adverse effects showed a very good tolerability of DUP 996.[1]


  1. EEG brain mapping in evaluating the time-course of the central action of DUP 996--a new acetylcholine releasing drug. Saletu, B., Darragh, A., Salmon, P., Coen, R. British journal of clinical pharmacology. (1989) [Pubmed]
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