Effects of the enkephalinase inhibitor SCH 34826 on the sleep-waking cycle and EEG activity in the rat.
The sedative effect of SCH 34826, an enkephalinase inhibitor, was evaluated by studying electroencephalographic (EEG) activity, behaviour and the sleep-waking cycle in the rat. The reference opioid, morphine, was used for comparison. After administration of morphine (10 mg/kg s.c.) the rats were motionless and stuporous at first and then hyperactive. An increase of slow wave sleep, at the expense of both wakefulness and REM sleep was recorded, with high-amplitude slow wave bursts appearing in the EEG tracings during the waking, albeit stuporous, phase. Relative spectral power in the 1-4 and 12-16 Hz bands was increased and there was a shift of the dominant frequency to a lower frequency. The specific opioid antagonist, naltrexone, readily reversed most of these effects. The drug SCH 34826 (10-100 mg/kg p.o.) had no effect on the parameters examined; large doses (300 and 1000 mg/kg p.o.) induced restlessness in some animals, resulting in increased waking. This effect was antagonized by naltrexone. The data indicate that SCH 34826, at doses far greater than those proposed for clinical use, is devoid of sedative liability and does not induce any of the behavioural or EEG effects typical of morphine.
Trampus
M
M
Research Laboratories, Schering-Plough S.p.A., Milan, Italy.
Conti
A
A
Marzanatti
M
M
Monopoli
A
A
Ongini
E
E
D000818:Animals; D004148:Dioxolanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D015244:Thiorphan / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects*
D004148:Dioxolanes; D004149:Dioxoles; D004151:Dipeptides; C056319:Sch 34826; D009271:Naltrexone; D009020:Morphine; D015244:Thiorphan; D015260:Neprilysin