title: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia.
abstract: BACKGROUND
  The alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is associated with genetic transmission of schizophrenia and related cognitive and neurophysiological sensory gating deficits. Cognitive dysfunction is responsible for significant psychosocial disability in schizophrenia. Nicotine, a low-potency agonist at the alpha7 receptor, has some positive effects on neurophysiological and neurocognitive deficits associated with schizophrenia, which suggests that more effective receptor activation might meaningfully enhance cognition in schizophrenia.
  
  
  OBJECTIVE
  To determine if 3-[(2,4-dimethoxy)benzylidene]anabaseine (DMXB-A), a natural alkaloid derivative and a partial alpha7 nicotinic cholinergic agonist, significantly improves neurocognition, and to assess, by effects on P50 auditory evoked potential inhibition, whether its neurobiological actions are consistent with activation of alpha7 nicotinic receptors.
  
  
  METHODS
  Randomized, double-blind crossover trial of 2 drug doses and 1 placebo.
  
  
  METHODS
  General clinical research center.
  
  
  METHODS
  Twelve persons with schizophrenia who did not smoke and were concurrently treated with antipsychotic drugs. One person was withdrawn because of a transient decrease in white blood cell count.
  
  
  METHODS
  Administration of DMXB-A.
  
  
  METHODS
  Total scale score of the Repeatable Battery for the Assessment of Neuropsychological Status and P50 inhibitory gating.
  
  
  RESULTS
  Significant neurocognitive improvement was found on the Repeatable Battery for the Assessment of Neuropsychological Status total scale score, particularly for the lower DMXB-A dose compared with placebo. Effects were greater than those of nicotine in a similar study. Significant improvement in P50 inhibition also occurred. Patients generally tolerated the drug well.
  
  
  CONCLUSIONS
  An alpha7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia. Longer trials are needed to determine the clinical utility of this novel treatment strategy.
authors.affiliation: Department of Veterans Affairs Schizophrenia Research Center, Denver, Colorado, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Josette G
authors.initials: JG
authors.lastname: Harris
authors.forename: Lynn L
authors.initials: LL
authors.lastname: Johnson
authors.forename: Vicki
authors.initials: V
authors.lastname: Pender
authors.forename: Susan
authors.initials: S
authors.lastname: Kongs
authors.forename: Diana
authors.initials: D
authors.lastname: Allensworth
authors.forename: Jamey
authors.initials: J
authors.lastname: Ellis
authors.forename: Gary O
authors.initials: GO
authors.lastname: Zerbe
authors.forename: Sherry
authors.initials: S
authors.lastname: Leonard
authors.forename: Karen E
authors.initials: KE
authors.lastname: Stevens
authors.forename: James O
authors.initials: JO
authors.lastname: Stevens
authors.forename: Laura
authors.initials: L
authors.lastname: Martin
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Adler
authors.forename: Ferenc
authors.initials: F
authors.lastname: Soti
authors.forename: William R
authors.initials: WR
authors.lastname: Kem
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
mesh_terms: D000328:Adult; D001597:Benzylidene Compounds / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index
chemical_list: D001597:Benzylidene Compounds; D018722:Nicotinic Agonists; D010919:Placebos; D011725:Pyridines; D011978:Receptors, Nicotinic; C088936:3-(2,4-dimethoxybenzylidene)anabaseine