Archival ReportClinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo
Section snippets
Subjects
We recruited six women and five men with no current medical problems and no psychiatric history, including ADHD. Medical and psychiatric history, review of systems, the structured interview for the DSM (17), and a physical examination were performed by a board-certified psychiatrist (JH). Laboratory tests and electrocardiogram were used to rule out any unknown medical condition. All subjects were stimulant-naive, with no history of exposure to amphetamines, cocaine, ecstasy, or MPH. Urine drug
Demographic and Radiotracer Characteristics
The mean age was 34 ± 8 years, and the mean body mass index was 28 ± 5 kg/m2. Radiotracer characteristics are summarized in Table 1. MPH was well tolerated, and only one subject experienced transient anxiety after the 40-mg dose. The 75- and 195-min plasma levels of the active enantiomer d-threo-MPH were 1.5 ± 1.2 and .6 ± .4 ng/mL (2.5 mg), 3.1 ± 3 and 2.8 ± 1.7 ng/mL (10 mg), and 22.9 ± 13.9 and 15 ± 4.4 ng/mL (40 mg), respectively. For correlation between plasma levels of d-threo-MPH and MPH
MPH Occupancy of NET
This is the first in vivo study in humans showing that clinically relevant doses of MPH occupy significant levels of NET. Although MPH has been used for the treatment of ADHD for decades, the exact mechanism of action is unclear. Stimulants enhance synaptic concentrations of DA and NE, d-amphetamine by increasing catecholamine release, and MPH by inhibiting catecholamine reuptake. Currently, it is believed that MPH's therapeutic effects in ADHD are due mostly to its DAT inhibition; however,
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2023, Behavioural Brain ResearchCitation Excerpt :High doses of methylphenidate also increase dopamine within the prefrontal cortex [34]. In addition, therapeutic doses of methylphenidate block around 70–80% of the norepinephrine transporters [29], resulting in an increase of extracellular norepinephrine in the brain [66]. Both dopamine and norepinephrine modulate the activity of several brain structures, including the prefrontal cortex, hippocampus, and striatum, being involved in a plethora of cognitive, reward, motivational, and behavioral processes [6,30,49].
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