Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats.
The encephalographic (EEG) properties of zaleplon were investigated in comparison with those of other sedative hypnotics in conscious rats with chronically implanted electrodes. The oral administration of zaleplon (0.25-1.0 mg/kg), triazolam (0.0625-0.25 mg/kg), zopiclone (1.0-4.0 mg/kg), brotizolam (0.0625-0.25 mg/kg), and nitrazepam (0.125-0.5 mg/kg) lengthened the total sleep in a dose-dependent manner. On distribution of sleep-wakefulness stages, zaleplon, in particular, increased the slow wave deep sleep (SWDS), whereas triazolam, brotizolam, and nitrazepam increased the slow wave light sleep (SWLS) in a dose-dependent manner. Zopiclone significantly increased the SWDS at a dose of 2 mg/kg and both the SWLS and the SWDS at a dose of 4 mg/kg. All tested hypnotics caused no influence on fast wave sleep (FWS) at doses tested. The appearance of the sleep-inducing activity of zaleplon was more rapid than those of any compounds tested, and zaleplon significantly increased the relative EEG power density in the delta frequency band over that of triazolam at 20 and 30 min after the administration in the spectral analysis. Therefore, the present findings suggest that the non-benzodiazepine zaleplon can be expected to exhibit high practical potential as a hypnotic and is characterized by an increase in SWDS with rapid onset of hypnotic action.
Noguchi
Hideaki
H
Medical Research Laboratories, Wyeth Lederle (Japan), Ltd, Saitama, Japan. NoguchH@wyeth.com
Kitazumi
Kazuhiro
K
Mori
Megumi
M
Shiba
Toshiharu
T
D000081:Acetamides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D053961:Azabicyclo Compounds; D002540:Cerebral Cortex / Q000502:physiology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009567:Nitrazepam / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D014229:Triazolam / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D034941:Upper Extremity / Q000294:innervation
D000081:Acetamides; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011743:Pyrimidines; C515050:zopiclone; D014229:Triazolam; D009567:Nitrazepam; C085665:zaleplon