linguistic:translation
Pharmacodynamics

There exist some paradoxical findings that oppose the notion that methylphenidate acts as silent antagonist of the DAT (DAT inhibitor). DAT occupancy of 80% is necessary for methylphenidate's euphoriant effect, but re-administration of methylphenidate beyond this level of DAT occupancy has been found to produce similarly potent euphoriant effects (despite DAT occupancy being unchanged with repeated administration). By contrast, other DAT inhibitors such as bupropion have not been observed to exhibit this effect. These observations, among others, have prompted the hypothesis that methylphenidate may actually act as a "DAT inverse agonist" or "negative allosteric modifier of the DAT" by reversing the direction of the dopamine flux by the DAT at higher dosages rather than by acting as a simple competitive transporter blocker.