Comparative effects of modafinil and amphetamine on daytime sleepiness and cataplexy of narcoleptic dogs.
The effects of modafinil and amphetamine on daytime sleep (polysomnographic recordings) and cataplexy (the food-elicited cataplexy test) were compared using the narcoleptic canine model. Results indicate that both modafinil (5 and 10 mg/kg body weight i.v.) and amphetamine (100 and 200 micrograms/kg i.v.) increase wakefulness and reduce slow-wave sleep in control and narcoleptic dogs. In contrast, the results of cataplexy testing demonstrate that amphetamine (2.5-160 micrograms/kg i.v.), but not modafinil (0.125-8.0 mg/kg i.v.) significantly suppresses canine cataplexy. These results suggest that the pharmacological property of modafinil is distinct from amphetamine. Results of polysomnographic recordings also demonstrate that narcoleptic dogs slept significantly more during the daytime than control dogs and required very high doses (10 mg/kg i.v. modafinil; 200 micrograms/kg i.v. amphetamine) of stimulants to reduce their level of sleepiness to that of control dogs. This finding is consistent with the data collected in human narcolepsy and validates the use of this canine model for the screening of stimulant compounds.
Shelton
J
J
Sleep Research Center, Stanford University School of Medicine, Palo Alto, California 94304, USA.
Nishino
S
S
Vaught
J
J
Dement
W C
WC
Mignot
E
E
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002385:Cataplexy / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy*; D012894:Sleep Stages; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000661:Amphetamine; D000077408:Modafinil