Preliminary studies on the structure-activity and time-effect relations of the central stimulating effects of modafinil in mice.
OBJECTIVE
To observe the structure-activity and time-effect relations of the central stimulating effects of modafinil for further pharmaceutical design and development and rational use of this kind of stimulant.


METHODS
Male mice served as subjects. The experiment was divided into two parts: 1) comparison between the dose (60, 120, 240 mg/kg) and temporal features of the effects of modafinil and its two derivatives on locomotor activity of mice; 2) Observation of the stimulating effects of modafinil (120 mg/kg) given during the day or night.


RESULTS
Modafinil could significantly increase the locomotor activity of mice in a dose-dependent way, the effect was best observed at the concentration of 120 mg/kg. The stimulating action of modafinil was increased by chlorination, but decreased by methylation. The central stimulating effect of modafinil showed no significant circadian difference.


CONCLUSIONS
The central stimulating effect of modafinil shows dose and time-related features. The effect tends to be enhanced by Chlorination but reduced by methylation.
Institute of Aviation Medicine, Beijing.
Hao
H
Zhan
Gui-xiang
GX
Tang
Yi-mei
YM
Xin
Yan-feng
YF
Li
Tong
T
Li
Sh-huang
ShH
Wei
Bao-chun
BC
Mu
Guang-qing
GQ
Lei
D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil