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

Abstract

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 temporooccipital, 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.

KCNQ Modulators Reveal a Key Role for KCNQ Potassium Channels in Regulating the Tone of Rat Pulmonary Artery Smooth Muscle

“…In our study, systemic pressure was unchanged or even decreased at the highest dose of linopirdine. We cannot explain the discrepancy, but our findings concur with reports that linopirdine does not affect blood pressure in humans (Saletu et al, 1989;Pieniaszek et al, 1995).…”

Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury

“…Results of electroencephalograms, ECGs, and clinical laboratory evaluations were not affected (Pieniaszek et al, 1995). Another study administering single oral doses of 30 mg linopirdine observed electroencephalography changes suggesting vigilance-improving properties and no abnormalities in ECG or laboratory evaluations, indicating a good tolerability (Saletu et al, 1989). Although the highest plasma levels were approximately 1.5 mM in those experiments compared with 10 mM of linopirdine in our in vitro experiments, this indicates a potential for clinical use of K V 7 blockers.…”

K+ Channel Modulators for the Treatment of Neurological Disorders and Autoimmune Diseases

“…94 Linopirdine was regarded as a promising drug because it enhanced the release of acetylcholine in cholinergic nerve terminals in the brain only when its release was triggered and improved learning and memory in rodents and primates. Although clinical trials with linopirdine remained largely inconclusive 95 or showed that it did not improve memory performance in elderly subjects, 96 linopirdine became a valuable pharmacological tool.…”