RT Journal
A1 Olincy A, Harris JG, Johnson LL, et al
T1 PRoof-of-concept trial of an α7 nicotinic agonist in schizophrenia
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2006
FD June 1
VO 63
IS 6
SP 630
OP 638
DO 10.1001/archpsyc.63.6.630
UL http://dx.doi.org/10.1001/archpsyc.63.6.630
AB Context 
    The α7 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 α7 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.Objectives 
    To determine if 3-[(2,4-dimethoxy)benzylidene]anabaseine (DMXB-A), a natural alkaloid derivative and a partial α7 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 α7 nicotinic receptors.Design 
    Randomized, double-blind crossover trial of 2 drug doses and 1 placebo.Setting 
    General clinical research center.Patients 
    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 One person was withdrawn because of a transient decrease in white blood cell count.Intervention 
    Administration of DMXB-A.Main Outcome Measures 
    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 α7 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.