Effects of bretazenil vs. zolpidem and placebo on experimentally induced sleep disturbance in healthy volunteers.
The effects of bretazenil 0.25 and 0.5 mg, a partial agonist at the benzodiazepine receptor, on sleep electroencephalogram (EEG), subjective sleep quality and morning psychomotor performance were compared to zolpidem 10 mg and placebo using noise as an experimental sleep disturbing factor in a single dose, double-blind, crossover study. Twelve healthy volunteers were subjected to prerecorded traffic noise with a mean sound level of 52 dB(A) during eight hours in bed. Significant effects of noise were found on sleep electroencephalogram (EEG) parameters (rapid eye movement [REM] sleep, stage 2 sleep and number of arousals), and subjective sleep quality assessments, but not on psychomotor performance (choice reaction time, digit span memory, and symbol digit substitution). Both drugs reduced the number of shifts between sleep stages and the number of arousals and increased REM sleep latency. Only after 0.5 mg bretazenil, stage 2 sleep increased and REM sleep decreased. Both doses of bretazenil significantly affected performance in the symbol digit substitution test. Sleep quality improved under drug treatments compared to placebo. The results suggest that experimental sleep disturbance can be a valuable tool in the investigation of potential sleep promoting compounds.
Gieschke
R
R
Department of Clinical Pharmacology, F. Hoffmann-La Roche, Basel, Switzerland.
Cluydts
R
R
Dingemanse
J
J
De Roeck
J
J
De Cock
W
W
D000328:Adult; D000704:Analysis of Variance; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009624:Noise, Transportation / Q000009:adverse effects; D017286:Polysomnography / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012894:Sleep Stages / Q000187:drug effects; D012893:Sleep Wake Disorders / Q000188:drug therapy* / Q000209:etiology; D012895:Sleep, REM / Q000187:drug effects; D000077334:Zolpidem
D001570:Benzodiazepinones; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; C054626:bretazenil