Objectives: Psychostimulants have been the standard pharmacotherapies for the treatment of attention-deficit/hyperactivity
disorder (ADHD), but are associated with abuse potential. Atomoxetine, a non-amphetamine,
selective norepinephrine reuptake inhibitor, is approved as a treatment for ADHD.
Receptor binding, preclinical behavioral, and human laboratory studies of the abuse
liability of atomoxetine are summarized.
Methods: Binding affinities of atomoxetine were determined for monoamine transporters and
other neurotransmitter-related receptors, ion channels, and transporter binding sites.
The potential stimulant effects of atomoxetine were evaluated preclinically in a mouse
locomotor activity study. Drug discrimination studies using rats, pigeons, and monkeys
were reviewed, and self-administration studies using monkeys trained to discriminate
cocaine or methamphetamine or self-administer cocaine were conducted. Additionally,
a human laboratory study was conducted to examine the subjective, physiological, and
psychomotor effects of atomoxetine, as compared to placebo, desipramine, phentermine,
and methylphenidate.
Results: Atomoxetine is a potent inhibitor of the presynaptic norepinephrine transporter with
minimal affinity for dopamine transporters or actions at GABAA receptors. Atomoxetine
did not stimulate locomotor activity in mice. In drug discrimination studies, atomoxetine
produced a profile similar to that of drugs without abuse liability. Atomoxetine,
like desipramine and in contrast to methylphenidate and amphetamine, did not maintain
self-administration in monkeys and was not preferred over food delivery up to doses
that decreased response rates, consistent with limited reinforcing strength. Results
from human drug abusers indicated that atomoxetine has significantly less abuse liability
than methylphenidate and phentermine, and no greater abuse liability than desipramine.
Conclusion: Data from receptor binding, preclinical behavioral, and human laboratory studies
suggest that atomoxetine lacks abuse potential is not an amphetamine-like agent.