Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men.
Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinie in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal alpha7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for the alpha7 subtype of the nicotinic cholinergic receptor in these processes. Rodent studies also demonstrated the efficacy of a selective partial alpha7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for alpha7 nicotinic activity may have utility in treating certain symptoms of schizophrenia.
Olincy
Ann
A
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. ann.olincy@uchsc.edu
Stevens
Karen E
KE
D000818:Animals; D001597:Benzylidene Compounds / Q000627:therapeutic use*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006801:Humans; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001597:Benzylidene Compounds; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088936:3-(2,4-dimethoxybenzylidene)anabaseine
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