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Modafinil (Provigil, Alertec, Modavigil, Modalert, Modiodal, Modafinilo, Carim, Vigia) is a mild analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration (FDA) for the treatment of narcolepsy, shift work sleep disorder,[1][2] and excessive daytime sleepiness associated with obstructive sleep apnea.[3] The European Medicines Agency has recommended that in Europe it be prescribed only for narcolepsy.[4]

Despite extensive research into the interaction of modafinil with a large number of neurotransmitter systems, a precise mechanism or set of mechanisms of action remains unclear.[5][6] It seems that modafinil, like other stimulants, increases the release of monoamines, specifically the catecholamines norepinephrine and dopamine, from the synaptic terminals. However, modafinil also elevates hypothalamic histamine levels,[7] leading some researchers to consider Modafinil a "wakefulness promoting agent" rather than a classic amphetamine-like stimulant (as evidenced by the difference in c-Fos distribution caused by modafinil as compared to amphetamine).[8] Despite modafinil's histaminergic action, it still partially shares the actions of amphetamine-class stimulants due to its effects on norepinephrine and dopamine.

A National Institute on Alcohol Abuse and Alcoholism (NIAAA) study highlighted "the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations" due to the drug's effect on dopamine in the brain's reward center.[9] However, the synergistic actions of modafinil on both catecholaminergic and histaminergic pathways lowers abuse potential as compared to traditional stimulant drugs while maintaining the effectiveness of the drug as a wakefulness promoting agent. Studies have suggested that modafinil "has limited potential for large-scale abuse"[10] and "does not possess an addictive potential in naive individuals."[11]

Modafinil was shown to be an effective treatment for attention deficit hyperactivity disorder (ADHD),[12] however in 2006 it was found by the FDA to be unfit for use by children for that purpose. It was rejected primarily due to one suspected case of Stevens-Johnson syndrome.[13][14][15][16] Cephalon's own label for Provigil now discourages its use by children for any purpose.[12] Other potentially effective, but unapproved targets include the treatment of depression,[17] opiate[18] & cocaine dependence,[19] Parkinson's disease,[20] schizophrenia,[21] and disease-related fatigue,[22][23] as well as fatigue that is the side effect of another medication.[24]

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