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PMID: 17689498 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.

Biochemical pharmacology ·Vol. 74 ·No. 8 ·2007-10-15 ·Pages 1212-23

Wilens TE, Decker MW

Abstract

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.

MeSH Terms
Animals Attention Deficit Disorder with Hyperactivity/drug therapy Cognition/drug effects Humans Isoxazoles/therapeutic use Nicotinic Agonists/pharmacology,therapeutic use Pyridines/therapeutic use Pyrrolidines/therapeutic use Receptors, Nicotinic/drug effects,physiology Synaptic Transmission
Chemicals
Isoxazoles Nicotinic Agonists Pyridines Pyrrolidines Receptors, Nicotinic 3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole pozanicline
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wilens Timothy E
Massachusetts General Hospital, Pediatric Psychopharmacology Research Unit, Yawkey Center for Outpatient Care-YAW 6A, Boston, MA 02114, USA. [email protected]
Decker Michael W
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Article Info
Journal
Biochemical pharmacology
Abbr.
Biochem Pharmacol
ISSN
0006-2952
DOI
10.1016/j.bcp.2007.07.002
Email
[email protected]
Published
2007-10-15
Epub
2007-00-07
Pages
1212-23
Language
English
Region
England
NLM ID
0101032
PMCID
PMC2974320
Subset
IM
Grants
NIDA NIH HHS · R01 DA012945-06A2 · United States
NIDA NIH HHS · K24 DA016264-02 · United States
NIDA NIH HHS · R01 DA012945 · United States
NIDA NIH HHS · K24 DA016264 · United States
NIDA NIH HHS · 2 R01 DA12945-06 · United States
NIDA NIH HHS · 5 K24 DA01624-02 · United States
External Links
PubMed source DOI: 10.1016/j.bcp.2007.07.002 PMC Full Text View journal details
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