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Modafinil is generally well-tolerated but can have potential risks and side effects. Common adverse effects of modafinil, experienced by less than 10% of users, include headaches, nausea, and reduced appetite. [92] [93] [20] Anxiety, insomnia, dizziness, diarrhea, and rhinitis are also reported in 5% to 10% of users. [20]
A Cephalon-founded study in which patients were administered modafinil, methylphenidate, and a placebo found that modafinil produces "psychoactive and euphoric effects and feelings consistent with [methylphenidate]." [12] Like modafinil, armodafinil is an inhibitor and/or inducer of certain cytochrome P450 enzymes.
Modafinil analogues acting as DRIs include both drugs similar to modafinil that affect dopamine without causing stimulant effects (atypical modafinil-like non-psychostimulant DRIs) such as flmodafinil and JJC8-016 and drugs that affect dopamine in a way similar to cocaine (classical or typical cocaine-like DRIs) such as JJC8-088.
The drug has been found to block the dopamine transporter (DAT) by 83%, to a greater extent than methylphenidate without unfavorable concomitant adrenergic effects. [8] The drug is an atypical DRI similarly to modafinil. [11] [1] [9] The affinities for the DAT of flmodafinil's enantiomers and modafinil have also been studied.
In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake enhanced executive function. [27] Modafinil does not improve mood or motivation in sleep-deprived or non-sleep deprived individuals. [28]
Adrafinil acts as a prodrug of modafinil and hence shares its mechanism of action. [13] Certain other drugs acting as atypical DRIs with known or potential wakefulness-promoting effects include solriamfetol (also a norepinephrine reuptake inhibitor), [14] [15] vanoxerine, [16] phenylpiracetam, [17] [18] [19] and mesocarb.
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Subsequently, more selective modafinil-derived DAT blockers, like JJC8-088 and JJC8-091, were developed. [1] [9] JJC8-088 has ~90-fold higher affinity for the DAT than JJC8-016 and ~2-fold lower affinity for the hERG. [9] Newer related modafinil analogues and DRIs with further reduced affinity for the hERG were also subsequently developed. [11]
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