A 7-year-old child with ADHD, combined presentation, is started on methylphenidate. His parents ask about the mechanism. Methylphenidate primarily acts by:

• A Blocking dopamine and norepinephrine reuptake transporters (DAT and NET) ✓
• B Blocking norepinephrine reuptake only in the locus coeruleus
• C Releasing dopamine from presynaptic terminals (amphetamine-like)
• D Acting as a dopamine D2 receptor agonist

Explanation

Methylphenidate blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), preventing the reuptake of these neurotransmitters from the synapse. This increases dopamine and norepinephrine levels in the prefrontal cortex, improving executive function, attention, and impulse control. Unlike amphetamines (which additionally cause release of catecholamines from presynaptic vesicles via VMAT2 displacement), methylphenidate is a pure reuptake inhibitor. Atomoxetine (a non-stimulant ADHD medication) primarily blocks NET without significant DAT blockade.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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