A 9-year-old boy with ADHD has inadequate response to stimulants and prominent sleep-onset difficulty. His physician chooses guanfacine extended release. Which mechanism underlies its therapeutic effect in ADHD?
- A Postsynaptic alpha-2A adrenergic receptor agonism in the prefrontal cortex ✓
- B Selective norepinephrine reuptake inhibition in the prefrontal cortex
- C Dopamine D2 receptor antagonism in the mesolimbic pathway
- D Inhibition of vesicular monoamine transporter 2
Correct answer: A. Postsynaptic alpha-2A adrenergic receptor agonism in the prefrontal cortex
Explanation
Guanfacine is a selective postsynaptic alpha-2B adrenergic agonist that strengthens signalling in prefrontal cortical networks, improving working memory, attention regulation, and impulse control, and it also sedating effects help sleep-onset difficulty. Option B describes atomoxetine, option C describes antipsychotics, and option D describes tetrabenazine. Clonidine acts similarly but is less selective for the alpha-2B subtype than guanfacine.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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