Atomoxetine, a Novel Treatment for Attention-Deficit-Hyperactivity Disorder

Alisa K. Christman, Pharm.D.; Joli D. Fermo, Pharm.D.; John S. Markowitz, Pharm.D.


Pharmacotherapy. 2004;24(8) 

In This Article

Mechanism of Action

The precise mechanism of action of atomoxetine in ADHD is unknown. Unlike traditional stimulant agents currently approved for ADHD in children and adults that work through increasing systemic levels of dopamine by binding to dopamine receptors in the brain, atomoxetine exerts its pharmacologic effect by the selective inhibition of the presynaptic norepinephrine transporter, therefore inhibiting the reuptake of norepinephrine. In the brain, the primary noradrenergic region is the locus ceruleus, an area that induces an alert waking state and enhances informational processing and attention to environmental stimuli.[13] In animal studies, the increased levels of dopamine and norepinephrine in the prefrontal cortex are necessary for optimal functioning.[8] Deficits of these neurotransmitters in the right dorsal prefrontal cortex affect attention regulation and inhibition to the response of distracting stimuli, whereas deficits in the right orbital prefrontal cortex are associated with immature behavior, lack of restraint, and increased motor activity.[8] In one study conducted in rats, atomoxetine increased extracellular levels of norepinephrine and dopamine in the prefrontal cortex of the brain 3-fold without concurrent increases in serotonin.[14] This study also found that atomoxetine did not increase the levels of dopamine in the striatum or nucleus accumbens, an action exerted by traditional psychostimulants, therefore suggesting that atomoxetine might pose a lower risk for drug abuse. Atomoxetine appears to have little affinity for other major neurotransmitter systems such as cholinergic, histaminergic, serotonergic, or β-adrenergic systems.[15]