Comparative study on the behavioral and EEG changes induced by diazepam, buspirone and a novel anxioselective anxiolytic, DN-2327, in the cat.
Behavioral and EEG effects of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-[(1,4)-dioxa-8-(azas piro-[4.5]dec-8- yl)carbonylmethyl]isoindolin-1-one (DN-2327; 1, 5 and 20 mg/kg p.o.) were compared to those of diazepam (0.2 and 1 mg/kg p.o.) and buspirone (1 and 5 mg/kg p.o.) in freely moving cats. DN-2327 did not affect motor coordination or the relative percentages of the three sleep-wakefulness stages. Diazepam (1 mg/kg) increased wakefulness and non-REM sleep, and buspirone (5 mg/kg) also increased wakefulness and decreased REM sleep. In addition, diazepam (1 mg/kg) caused severe motor disturbance, but buspirone did not. The cortical EEG power density spectra during wakefulness were changed almost dose-dependently by DN-2327 (decreased: 2-7.75 Hz; increased: 20-49.75 Hz), and dose-dependently by diazepam (decreased: 2-7.75 Hz; increased 13-49.75 Hz) and buspirone (decreased: 4-9.75 and 13-19.75 Hz). The effect of DN-2327 on the cortical EEG varied with the sleep-wakefulness stage. The power of the 4- to 7.75-Hz frequency (theta) band of the hippocampal EEG during wakefulness was decreased by diazepam and buspirone but not by DN-2327, while the peak frequency of its spectra was decreased only by diazepam. On the other hand, during non-REM sleep, DN-2327 decreased the power of the theta band as did diazepam. These results indicate that the behavioral and EEG effects of DN-2327 differ completely from those of buspirone and considerably from those of diazepam and that the EEG effect of DN-2327 varies with the sleep-wakefulness stage.
Research and Development Division, Takeda Chemical Industries Ltd., Osaka, Japan.
T
T
Hashimoto
C
C
Hamada
T
T
Wada
N
N
Fukuda
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001931:Brain Mapping; D002065:Buspirone / Q000494:pharmacology*; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects* / Q000295:instrumentation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005583:Fourier Analysis; D054833:Isoindoles; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects; D012815:Signal Processing, Computer-Assisted / Q000295:instrumentation*; D012894:Sleep Stages / Q000187:drug effects; D013141:Spiro Compounds / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009287:Naphthyridines; D011963:Receptors, GABA-A; D013141:Spiro Compounds; C060382:pazinaclone; D003975:Diazepam; D002065:Buspirone