Acute neurophysiological effects of the hypnotic zolpidem in healthy volunteers.
BACKGROUND
The imidazopyridine zolpidem is a hypnotic drug with relative selectivity for the benzodiazepine (BZP) type 1 receptor subtypes displaying a different biochemical structure to that of BZPs. Little is known of its electrophysiological effects.


OBJECTIVE
The aim of the present study was to investigate the acute neurophysiological effects of clinical oral doses of zolpidem.


METHODS
This was a double blind, independent group design study. Thirty-six young, healthy volunteers were randomly allocated to one of three groups--zolpidem (5 mg and 10 mg) and placebo. In addition to ERPs, behavioural measures were used to examine sedative effects of the drug.


RESULTS
ERPs were affected in a similar way to that described after sedative/hypnotic drug ingestion: increased N2 and P3 latencies and decreased N2 and P3 amplitudes. However, contrary to what is expected of a hypnotic drug, there was no change with N1 while P2 amplitude increased after the highest dose.


CONCLUSIONS
Because zolpidem showed different effects in different components, it seems to first enhance or preserve initial orienting (no change in N1), after an increase of P2 and then drastically diminish resource allocation (affecting N2 and P3 latencies and amplitudes). The study with ERPs, therefore, allows a more direct "moment to moment" investigation of finer mechanisms of changes in cerebral processes underlying the acute ingestion of the drug in question. The effects on N2 and P3 amplitudes and latencies were similar to those of other sedative/hypnotic drugs. However, zolpidem led to an unexpected increase in P2 amplitude; this effect may be related to its selective receptor binding profile and warrants further research.
Lucchesi
Lígia M
LM
Department of Psychobiology, Universidade Federal de São Paulo, SP, Brazil. ligia@psicobio.epm.br
Braga
Nadia I de O
NI
Manzano
Gilberto M
GM
Pompéia
Sabine
S
Tufik
Sergio
S
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem