Attention deficit hyperactivity disorder management
There are two major medications derived from methylphenidate's isomers: a racemic mixture of half d-threo-methylphenidate and half l-threo-methylphenidate called methylphenidate (Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called dexmethylphenidate (Focalin).
Modafinil
Against the hypothesis that modafinil exerts its effects by acting as a DRI, tyrosine hydroxylase inhibitors (which deplete dopamine) fail to block the effects of modafinil in animals. In addition, modafinil fails to reverse reserpine-induced akinesia, whereas dextroamphetamine, a dopamine releasing agent (DRA), is able to do so. Moreover, one of the first published structure-activity relationship studies of modafinil found in 2012 that DAT inhibition did not correlate with wakefulness-promoting effects in animals among modafinil analogues, and a variety of analogues without any significant inhibition of the DAT still produced wakefulness-promoting effects. Furthermore, "[the] neurochemical effects [of modafinil] and anatomical pattern of brain area activation differ from typical psychostimulants and are consistent with its beneficial effects on cognitive performance processes such as attention, learning, and memory", and a study found that modafinil-induced increased locomotor activity in animals was dependent on histamine release and could be abolished by depletion of neuronal histamine, whereas those of methylphenidate were not and could not be. As such, although it is established that modafinil is a clinically significant DRI, its full pharmacology remains unclear and may be more complex than this single property (i.e., may also include DAT-independent actions, such as "activation of the orexin system").