Awakening properties of modafinil: effect on nocturnal activity in monkeys (Macaca mulatta) after acute and repeated administration.
Single oral administration of modafinil (16-64 mg/kg) in monkeys induced an increase in nocturnal activity and in behavioural arousal without stereotyped behaviour. Modafinil-induced increase in nocturnal activity was prevented by the centrally acting alpha 1 adrenoceptor antagonist prazosin. After repeated oral administration of modafinil, b.i.d. for 5 days, nocturnal activity was still increased, but was lower than after a single administration; the gradual decrease appeared on the second night. No rebound of sleep and no residual effect on night 5 (when modafinil was administered for 4 days and placebo on day 5) were seen after the withdrawal of the drug. Therefore, modafinil appeared to produce strong behavioural stimulation and awakening in a non-human primate species, after single, as well as after repeated administration, without other obvious side-effects (no sign of anxiety, no behavioural trouble). These awakening properties involved a modulation (stimulation) of a central alpha 1 adrenergic system.
Hermant
J F
JF
Centre de Recherches du Laboratoire L. Lafon, Maisons-Alfort, France.
Rambert
F A
FA
Duteil
J
J
D000284:Administration, Oral; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil; D011224:Prazosin