Differential EEG effects of the anxiolytic drugs, deramciclane (EGIS-3886), ritanserin and chlordiazepoxide in rats.
The influence of serotonergic and benzodiazepine type anxiolytic drugs on the cortical activation and sleep-wakefulness cycle were compared by evaluating the effects of ritanserin and deramciclane (EGIS-3886), two 5-HT2 receptor antagonists, and chlordiazepoxide on the electroencephalogram (EEG) in freely moving rats. Following drug administration (1, 3, and 10 mg/kg, PO for all drugs), EEG was continuously sampled for 6 h and power spectra were calculated for every 5 s to assess changes in slow wave activity and sleep phases. In a separate test, anticonvulsant effects of the drugs were examined in mice. Both deramciclane and ritanserin slightly increased total time spent in deep sleep (DS) and lengthened sleep episodes. In contrast, chlordiazepoxide had a strong inhibitory action on DS, sleep time being shifted to more superficial light sleep (LS). The incidence and length of the high voltage spindle (HVS) episodes characteristic for the motionless, awake rat were increased at the highest dose of both deramciclane and ritanserin, while it was decreased by chlordiazepoxide. In mice, chlordiazepoxide had a marked anticonvulsant effect, while deramciclane was moderately effective and ritanserin ineffective. In conclusion, the 5-HT2 receptor antagonist anxiolytic drugs seem to be superior compared to the benzodiazepine type anxiolytic drug, chlordiazepoxide, as ritanserin and deramciclane improved sleep quality by increasing sleep episode length and time spent in DS, while chlordiazepoxide enhanced sleep fragmentation and decreased DS.
Détári
L
L
Department of Comparative Physiology, Eötvös Loránd University, Budapest, Hungary. detarineu@ludens.elte.hu
Szentgyörgyi
V
V
Hajnik
T
T
Szénási
G
G
Gacsályi
I
I
Kukorelli
T
T
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D016713:Ritanserin / Q000494:pharmacology; D012894:Sleep Stages / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001892:Camphanes; D016713:Ritanserin; D002707:Chlordiazepoxide; C060555:deramciclane