The precise mechanism of action of methylphenidate is not known.
Even some of the most fundamental issues continue to be debated.
Much of the research into the mechanism of action of
methylphenidate is brought together in a recent publication
(Solanto, Arnsten, & Castellanos
2001)
It has often been assumed that stimulants act on dopamine
transmission in the prefrontal cortex. It has been hypothesised
that ADHD symptoms arise from a dopamine insufficiency in the
prefrontal cortex and that stimulants act to increase dopamine
release, thus normalising function. While this assumption is rarely
challenged, there are little data using low dose oral stimulants to
either support or refute it. Data from PET studies have
demonstrated that methylphenidate preferentially binds to dopamine
transporters in the striatum rather than in the prefrontal cortex
and it may be the case that methylphenidate has effects in both the
striatum and cortex.
It now also seems likely that both dopaminergic and
noradrenergic transmission are involved in the pathogenesis of ADHD
and in the mechanism of action of methylphenidate.