Potential noradrenergic targets for cognitive enhancement in schizophrenia.
Substantial evidence suggests that alterations in noradrenergic function contribute to the cognitive impairments of schizophrenia. Activation of post-junctional alpha 2a-adrenergic receptors in the prefrontal cortex by the alpha 2a-selective agonist guanfacine has demonstrated some preliminary benefit in subjects with schizophrenia treated with atypical antipsychotics. alpha 1-adrenergic receptor activity may be less important in mediating the cognitive impairments of schizophrenia. beta-adrenergic receptors may serve as another potential target for cognitive remediation in schizophrenia. However, the potential increase in memory consolidation in schizophrenia patients produced by beta-adrenergic agonists may be outweighed by the impairment in cognitive flexibility and executive functioning produced by beta-adrenergic agonists. Finally, norepinephrine reuptake inhibitors, such as atomoxetine, hold promise as potential cognitive enhancers in schizophrenia because of their ability to indirectly but selectively increase extracellular dopamine concentrations in the prefrontal cortex.
Friedman
Joseph I
JI
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. jfriedman1@rcn.com
Stewart
Daniel G
DG
Gorman
Jack M
JM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D016316:Guanfacine / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects; D011437:Propylamines / Q000494:pharmacology* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications* / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D011437:Propylamines; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride; D009638:Norepinephrine