Mechanism profile for arousal effects of modafinil

Abstract

Abstract: Modafinil is a potent wake-promoting compound with low abuse potential used in the treatment of narcolepsy and day time sleepiness. The compound is reported to affect multiple neurotransmitter systems such as catecholamines, serotonin, glutamate, GABA, orexin, and histamine, however, the molecular mechanism by which modafinil increases wakefulness is debated. It was previously testified that arousal effects of modafinil were not exhibited in dopamine transporter KO mice; furthermore, treatment of dopamine (DA) D₂ receptor (D₂R)-deficient mice with D₁R-specific antagonists completely abolished arousal effects of modafinil. These findings strongly indicate that dopamine and dopaminergic D₁R and D₂R are essential for the wakefulness caused by modafinil, and its influence on other neurotransmitter systems may result from enhanced dopaminergic activity and wakefulness.This review summarizes the progress on mechanism profile for arousal effects of modafinil.

Key words: Modafinil, Wakefulness, Dopamine, Dopamine D₁ receptor, Dopamine D₂ receptor, DA transporter

CLC Number:

R749

CHEN Chang-rui, QU Wei-min, HUANG Zhi-li. Mechanism profile for arousal effects of modafinil[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(12): 1428-1433.

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