Introduction: Racemate of d/l-threo-methylphenidate (MPH; Ritalin) is an effective first-line treatment
for the symptoms associated with attention-deficit/hyperactivity disorder (ADHD).
Although MPH has long been administered as a racemic mixture of the two enantiomers,
d-MPH and l-MPH, converging lines of evidence drawn from investigations using in vitro
systems indicate that it is predominantly, d-threo MPH which mediates the pharmacological/therapeutic
actions of MPH. Aim: In the present study, we investigated which of the two enantiomers has stronger effects
on the tyrosine hydroxylase (TH) and monoamine-oxidase B (MAO-B) enzyme activity in
vitro, as both enzymes are important for dopamine efficacy. Methods: Using homogenates of rat pheochromocytoma cells (PC-12) we investigated dose dependent
effects of d-threo and l-threo MPH. Homogenates were treated with 0/1/10/100 nM and
1/10/100 µM of each MPH enantiomer. TH activity was detected via high-performance
liquid chromatography (HPLC) methodology, while MAO-B activity was measured using
fluorescent based enzyme-linked immunosorbent assay (ELISA). Results: We could observe dose dependent higher TH as well as MAO-B activity after treatment
with d-threo MPH compared to l-threo MPH. Discussion: This exploratory investigation revealed in vitro pharmacological evidence for a potential
difference between MPH enantiomers on dopaminergic enzyme activity. This finding might
point to the therapeutic effects in the treatment of ADHD.
