Attention deficit/hyperactivity disorder (
ADHD) is the most commonly diagnosed neurobehavioral disorder in children and adolescents, and in about half of these patients, significant symptomology continues into adulthood. Although impulsivity and hyperactivity are the most salient features of
ADHD, cognitive deficits, particularly impairments in attention and executive function, are an important component, particularly in adolescents and adults, with over 90% of adults seeking treatment for
ADHD manifesting
cognitive dysfunction. Currently available medications treat the core
ADHD symptoms but typically do not adequately address cognitive aspects of
ADHD, underscoring the need for new
therapeutics.
Dopamine and
norepinephrine are hypothesized to be particularly important in
ADHD, but there is emerging evidence that
cholinergic neurotransmission, particularly involving neuronal
nicotinic acetylcholine receptors (nAChRs), may play a role in the pathophysiology of
ADHD.
Nicotine has demonstrated procognitive effects in both humans and experimental animals and has produced signals of efficacy in small proof-of-concept adult
ADHD trials. Although adverse effects associated with
nicotine preclude its development as a therapeutic, a number of novel nAChR agonists with improved safety/tolerability profiles have been discovered. Of these,
ABT-418 and
ABT-089 have both demonstrated signals of efficacy in adults with
ADHD. Notably, tolerability issues that might be expected of a nAChR agonist, such as
nausea and
emesis, were not observed at efficacious doses of
ABT-089. Further understanding of the effects of novel neuronal nAChR agonists on specific aspects of cognitive functioning in
ADHD is required to assess the full potential of this approach.