Atomoxetine: The First Nonstimulant for the Management of Attention-Deficit/Hyperactivity Disorder

Shelby L. Corman; Bethany A. Fedutes; Colleen M. Culley


Am J Health Syst Pharm. 2004;61(22) 

In This Article


Atomoxetine is a methylphenoxy-benzenepropanamine derivative with antidepressant activity. Although the precise mechanism of action is unknown, atomoxetine is thought to enhance noradrenergic function via selective inhibition of the presynaptic norepinephrine transporter.[11] Atomoxetine has little affinity for muscarinic, serotonergic, cholinergic, or adrenergic receptors.[8,11,12] Animal models have demonstrated that atomoxetine increases by threefold extracellular norepinephrine and dopamine concentrations in the prefrontal cortex, an area responsible for attention, judgment, self-monitoring, memory, motor sequences, and impulse control, but does not alter serotonin levels.[8] Thus, increasing noradrenergic transmission in cortical areas is theorized to be related to the efficacy of atomoxetine in ADHD. In addition, atomoxetine had no effect on the extracellular dopamine levels in the striatum or nucleus accumbens in animal models, a region associated with psychostimulation and the rewarding properties of abused drugs.[11]