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Milgram NW, Callahan H, Siwak C. 
“Adrafinil: A Novel Vigilance Promoting Agent”. 
CNS Drug Reviews. 1999;5(3):193-212.
Behavioral stimulants have widespread potential application in the treatment of affective disorders, disorders of vigilance, and disorders of sleep. Most behavioral stimulants, however, must be used with extreme caution because of undesirable side effects that include stereotypy, anxiolytic effects, and addiction. Adrafinil, developed in France by Louis Lafon Laboratories, is a novel pharmaceutical that has behavioral-activating effects but lacks the undesirable side effects of other stimulants. Peripheral sympathomimetic ef- fects are also absent in subjects treated with adrafinil. Jouvet (36) introduced the term "eugregorique" (eugregoric in English) to characterize this unique type of arousal-pro- ducing agent, but the term is not widely used in the scientific literature.1 There have not been many published studies on adrafinil, and the large majority of studies have been pub- lished in French. Human studies indicate that adrafinil has clinical efficacy as a vigilance-promoting and mood-enhancing agent in the elderly. As an area for therapeutic in- tervention, vigilance enhancement has received much more attention in Europe than in North America. Somewhat surprisingly, perhaps, adrafinil is known to a larger nonscienti- fic audience, where it is considered to be a nootropic agent.

The literature on modafinil, the primary metabolite of adrafinil is much more ex- tensive. This work has largely focused on the potential application of modafinil in the treatment of sleep disorders, and modafinil has recently received regulatory approval for the treatment of narcolepsy in the United States. Since the types of clinical trials that have been conducted differ (vigilance enhancement for adrafinil vs. narcolepsy for modafinil), it is not clear whether modafinil effectively replaces adrafinil or whether the two com- pounds are uniquely valuable for different applications. Most investigators assume that adrafinil and modafinil both serve as α 1-adrenergic–receptor agonists. The evidence in support of this hypothesis, however, is weak, and other mechanisms of action are probable. This review focuses primarily on adrafinil, but it also reviews studies on modafinil that help to clarify the underlying mechanisms of action of adrafinil. This review also considers potential novel applications of adrafinil in the treatment of disorders associated with dementia.
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