The present results corroborate studies on healthy volunteers showing that residual effects of hypnotics increase with their half-lives. The results further suggest that drugs preserving physiological EEG rhythms before and during the driving simulation test 9-11 h post-dose, such as zolpidem, do not influence next-day driving abilities.
The cognitive potential, P300, is a phenomenon frequently studied in relation to template matching of the brain. To understand the neurochemical mechanisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated application as well as after 1 week of withdrawal on the P300 and N200 waves in an auditory ‘odd-ball’ paradigm in three parallel groups of 10 healthy volunteers. Following single administration, both fluoxetine and clomipramine reduced (–39 ± 14%, p < 0.01) the peak amplitude of P300 at the Pz electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 ± 7% and 24 ± 11%, respectively, were found following 8 days of treatment, 2 h after administration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be significantly modified at the frontal scalp area 1 h after the tianeptine administration on day 8, whereas the postdosing changes induced by fluoxetine were localised in the midline and right centrotemporal scalp regions. Only minor reductions in peak latencies have been observed. It can be concluded that serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cholinergic systems. These results suggest that serotonin has a regulatory function in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.
Apomorphine, a dopamine receptor agonist (given in a dose of 0.75 mg s.c.), was administered to 8 healthy volunteers; electroencephalograph (EEG) and event-related potential (ERP) mapping were performed before dosing and 0.5, 1.5 and 2.5 h after dosing. Apomorphine caused an overall increase in beta activity at time 0.5 h in both absolute and relative energy; P300 and CNV ERPs were not significantly altered, although a tendency towards increased P300 latency was seen. The results confirm that the EEG mapping technique is sufficiently sensitive to monitor dopaminergic neurochemical stimulation by means of apomorphine. This could lead to a new, non-invasive and repeatable method for monitoring central neuronal systems which is more convenient to apply repeatedly than for example positron emission tomography techniques. Furthermore, electrophysiological techniques undoubtedly constitute an alternative to classical neuroendocrinological methods, allowing a more direct assessment of central nervous system neurotransmission. Finally, these EEG approaches could lead to better characterization of drugs acting on dopaminergic pathways, such as antipsychotics.
Quantitative pharmaco-EEG has become a useful technique for determing pharmacodynamic parameters after CNS-active drug administration. Nevertheless, one of the most important problems faced by practitioners of pharmaco-EEG is the difficulty in evaluating drug-specific effects. In this article, a methodology for comparing two time sequences of pharmacodynamic measurements, the Statistical Decision Tree (SDT), is proposed. This methodology, based on one- and multi-dimensional Wilcoxon signed-rank tests on EEG variables, takes into account vigilance fluctuations and placebo effects in order to pick out effects specifically due to the drug.
The pharmaco-EEG profile and the effects on P300 and CNV of befloxatone, a new selective and reversible MAO-A inhibitor, were assessed in a randomized, double-blind, placebo-controlled, 4-way crossover study. Twelve healthy young male volunteers were administered single doses of 2.5, 10 and 20 mg befloxatone and placebo separated by a 1-week washout. The EEG data were recorded before and at least 6 h after drug administration, by means of 28 leads allowing topographical analysis of the results. MAO inhibition, subjective effects and safety variables were also investigated. Statistical analysis was performed by means of the SDT method. Befloxatone induced dose-related EEG changes which occurred rapidly, peaked between 0.5 and 2 h and lasted at least until 6 h after drug administration. The EEG changes were characterized by an increase in absolute and/or relative alpha power, mainly alpha 1, after the 3 doses and a theta power increase after 10 and 20 mg only. These changes occurred mainly over the centroparietotemporal areas. Concerning the event-related potential, P300 latency of the auditory evoked potentials did not change. The P300 and CNV mean topographic amplitudes were decreased, between 0.5 and 2 h, after the two lowest doses for the P300 and the 3 doses for the CNV. After administration of 2.5, 10 and 20 mg, MAO inhibition was shown by respectively 38, 76 and 81% reduction in plasma free 3, 4-dihydroxyphenylglycol reached after 2–4 h. Such a pharmaco-EEG profile, occurring at doses inducing MAO-A inhibition, is similar to those already described with nonsedative antidepressants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.