Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/27235
Title: Flunitrazepam-induced changes in neurophysiological, behavioural, and subjective measures used to assess sedation
Authors: Lucchesi, L. M.
Pompeia, S.
Manzano, G. M.
Kohn, A. F.
Galduroz, JCF
Bueno, OFA
Tufik, S.
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Keywords: benzodiazepines
EEG
event-related
potentials
ERP
flunitrazepam
P300
sedation
Issue Date: 1-May-2003
Publisher: Elsevier B.V.
Citation: Progress in Neuro-psychopharmacology & Biological Psychiatry. Oxford: Pergamon-Elsevier B.V., v. 27, n. 3, p. 525-533, 2003.
Abstract: Introduction: Certain features of event-related potentials (ERPs), electroencephalographic (EEG), and behavioural measures vary with differing states of alertness and/or sedation. Purpose: This study was conducted to investigate changes in several measures usually viewed as reflecting states of sedation/sleepiness associated with the use of a range of doses of the hypnotic benzodiazepine (BZD) flunitrazepam (FNZ). Methods: This was a double blind, independent group design study of the effects of acute oral doses of FNZ in young healthy volunteers. Forty-eight subjects were randomly allocated to one of four groups-FNZ (0.6, 0.8, and 1.0 mg) and placebo (PLAC)-and tested prior to treatment and then in a posttreatment session close to the theoretical peak plasma concentration. ERP latencies and amplitudes were measured at midfrontal (Fz), midcentral (Cz), and midparietal (Pz) using a standard auditory oddball paradigm. EEG changes were assessed at Pz. Behavioural measures included the digit-symbol substitution test (DSST), a cancellation task (CT), and subjective ratings of alertness and attentiveness by the subjects (SUB) and the experimenter (EXP). Results: FNZ led to psychomotor impairments and decreased alertness and attention; these effects were consistent with previous findings. A progressive, dose-related increase in P3 latency occurred in Fz, Cz, and Pz, and there was an increase in N1 (Fz, Cz) and N2 (Fz). N2-P3 amplitude decreased in Fz. EEG power bands beta 1 increased for the two highest doses, but no significant differences were noted in theta, delta, and alpha bands. P3 latencies, experimenter-rated levels of alertness, and DSST scores differentiated all three doses of FNZ from PLAC. Conclusion: the most sensitive measures used were P3 latencies of the ERPs (which varied with FNZ dose), DSST, and the experimenter-rated levels of alertness. However, we found no evidence for the assumption that one single phenomenon was reflected in all measures and different mechanisms were probably involved. Further experiments will be needed for more in-depth probing of the finer mechanisms underlying sedation/sleepiness and how they affect behavioural and eletrophysiological measures of the central nervous system (CNS) function. (C) 2003 Elsevier Science Inc. All rights reserved.
URI: http://repositorio.unifesp.br/handle/11600/27235
ISSN: 0278-5846
Other Identifiers: http://dx.doi.org/10.1016/S0278-5846(03)00044-7
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