Differential effects of midazolam and zolpidem on sleep-wake states and epileptic activity in WAG/Rij rats.
Hypnotic drugs are known to possess antiepileptic activity. Therefore, the effects of the benzodiazepine hypnotic midazolam (10 mg/kg) and the novel imidazopyridine hypnotic zolpidem (10 mg/kg) on sleep-wake states and on the number of spike-wave discharges were evaluated in WAG/Rij rats. Rats of this strain are considered to be a model for generalized absence epilepsy. Animals were implanted with chronic monopolar EEG electrodes and, after recovery from surgery, the EEG was recorded for 6 h during the dark period on 3 consecutive days. Sleep recordings were analyzed using Hjorth's parameters and number and duration of spike-wave discharges were visually determined. It was found that both drugs facilitated nonREM sleep at the cost of wakefulness. Both hypnotics also reduced the number and duration of spike-wave discharges. The initial decrease after midazolam, however, was followed by a rebound reflecting a poorer quality of vigilance expressed as an increase in spike-wave discharges. The strong antiabsence activity of zolpidem mimics that of midazolam and is well correlated with their equipotent hypnotic action and anticonvulsant effect in the isoniazid test.
Depoortere
H
H
Synthélabo Recherche (L.E.R.S.), Bagneux, France.
Françon
D
D
van Luijtelaar
E L
EL
Drinkenburg
W H
WH
Coenen
A M
AM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*; D000077334:Zolpidem
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000077334:Zolpidem; D008874:Midazolam