title: AZD3480, a novel nicotinic receptor agonist, for the treatment of attention-deficit/hyperactivity disorder in adults.
abstract: BACKGROUND
  Laboratory studies have found that acute stimulation of nicotinic acetylcholine receptors improves cognition in adult attention-deficit/hyperactivity disorder (ADHD). Clinical trials of nicotinic agonists have been mixed, underscoring the need to understand the mechanisms for individual differences in clinical response. Using cognitive models within a clinical trial framework may provide insight into these differences.
  
  
  METHODS
  This was a within-subjects, randomized, placebo-controlled double-blind trial of the nicotinic agonist AZD3480 (also termed TC-1734) at doses of 5 mg and 50 mg and placebo in adults with ADHD. The order of the 2-week treatment periods was randomized, and a 3-week wash out separated each drug treatment period. Response inhibition (Stop Signal Task [SST]) and clinical efficacy (Investigator Rated Conners Adult ADHD Rating Scale [CAARS-INV]) were the a priori primary outcome measures of cognitive and clinical effects. We hypothesized that AZD3480 treatment would improve SST performance and clinical symptoms (CAARS-INV Total ADHD Symptoms Score).
  
  
  RESULTS
  Thirty subjects were randomized, with 24 included in the intent-to-treat analyses. SST performance and total ADHD symptoms were significantly improved with 50 mg of AZD3480. CAARS-INV ratings of inattention, memory problems, and emotional lability/impulsivity were significantly improved with 50 mg of AZD3480.
  
  
  CONCLUSIONS
  These results support previous work suggesting that nicotinic agonists are viable as treatments for adult ADHD. Measuring cognitive endophenotypes related to both the disorder and mechanism of treatment may help further rational drug development for dimensional features that cross-cut psychiatric disorders.
authors.affiliation: Clinical Neuroscience Research Unit, Department of Psychiatry, The University of Vermont, Burlington, Vermont. Electronic address: Alexandra.Potter@uvm.edu.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Potter
authors.affiliation: Targacept Inc, Winston-Salem, North Carolina.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dunbar
authors.affiliation: Clinical Neuroscience Research Unit, Department of Psychiatry, The University of Vermont, Burlington, Vermont.
authors.forename: Emily
authors.initials: E
authors.lastname: Mazzulla
authors.affiliation: Targacept Inc, Winston-Salem, North Carolina.
authors.forename: David
authors.initials: D
authors.lastname: Hosford
authors.affiliation: Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Newhouse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D011725:Pyridines; C490152:ispronicline
keywords: ADHD; AZD3480; Acetylcholine; cognition; nicotinic; therapeutic