Effects of four antiepileptic drugs on sleep and waking in the rat under both light and dark phases.
Sedation is a common side effect of anticonvulsant drug therapy. To find out whether the new antiepileptic drugs, felbamate and lamotrigine, are able to produce sedation, we carried out electroencephalographic (EEG) studies in the rat to measure drug effects on sleep-wake patterns, during both light and dark phases. For comparison, the reference drugs, carbamazepine and phenobarbital, were also studied. EEG activity was recorded for 6 h after oral (PO) administration of drugs or vehicle, and the stages of wakefulness, rapid eye movements (REM) sleep and non-REM sleep were classified thereafter. In the light phase, felbamate (30-300 mg/kg) did not produce sedative effects, while lamotrigine (3-30 mg/kg) increased wakefulness at each dose tested. Carbamazepine (10-100 mg/kg) did not produce sleep-wake alterations, and phenobarbital (100 mg/kg) markedly suppressed REM. In the dark phase, felbamate (300 mg/kg), lamotrigine (30 mg/kg), and carbamazepine (100 mg/kg) reduced REM but did not change the total amount of sleep. Phenobarbital, at 100 mg/kg, markedly increased total sleep and greatly reduced REM. This study shows that the anticonvulsant drugs examined have different effects on the states of sleep and wakefulness in the rat. The data are discussed on the basis of the mechanism of action that characterizes each individual drug.
Bertorelli
R
R
Research Laboratories, Schering-Plough, Milan, Italy.
Ferri
N
N
Adami
M
M
Ongini
E
E
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000078328:Felbamate; D000077213:Lamotrigine; D008297:Male; D048448:Phenylcarbamates; D010775:Photic Stimulation; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D048448:Phenylcarbamates; D011409:Propylene Glycols; D014227:Triazines; D002220:Carbamazepine; D000077213:Lamotrigine; D000078328:Felbamate