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Annotation

Bodnar AL, Cortes-Burgos LA, Cook KK, Dinh DM, Groppi VE, Hajos M, Higdon NR, Hoffmann WE, Hurst RS, Myers JK, Rogers BN, Wall TM, Wolfe ML, Wong E. Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors. J Med Chem . 2005 Feb 24 ; 48(4):905-8. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Ann Olincy
Submitted 5 July 2006 Posted 5 July 2006

This compound looks promising because it has good bioavailability and passes through the blood-brain barrier. It differs from DMXB-A in that it is a full agonist, which some people believe targets the α7 nicotinic receptor more fully, but also may have more problems with desensitization, which is not tested in this paper. They administer the drug to animals that are pretreated with amphetamine to cause a sensorimotor gating deficit, and thereby an animal model of schizophrenia. (I favor the use of DBA mice, which are abnormal in their gating because genetically they have fewer nicotinic receptors, as is the case with people with schizophrenia.) The authors are able to correct the gating deficit with their drug. However, they do not then let the deficit become abnormal (or artificially induce the abnormality again) and then give a second dose of their drug to see if they can again get a response, which would show that the receptor does not desensitize and the drug will work with repeated dosing. This is the problem with nicotine. We were able to get a second response with...  Read more


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Comments on Related News
Related News: Nicotinic Receptor Agonist Shows Promise in Pilot Study

Comment by:  Robert W. Buchanan
Submitted 5 July 2006 Posted 5 July 2006

In light of the limitations of first- and second-generation antipsychotics and other pharmacological agents for the treatment of cognitive impairments in schizophrenia, the demonstration of an acute benefit of DMXB-A for cognitive performance and sensory gating is of considerable potential interest. Patients with schizophrenia are characterized by a broad range of cognitive impairments (Nuechterlein et al., 2004). These impairments have been shown to be a major determinant of poor functional outcome (Green et al., 2004). The NIMH has made a substantial commitment to facilitate the development of new pharmacological treatments for cognitive impairments through their funding of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia   Read more


View all comments by Robert W. Buchanan

Related News: Nicotinic Receptor Agonist Shows Promise in Pilot Study

Comment by:  Patricia Estani
Submitted 6 July 2006 Posted 6 July 2006
  I recommend the Primary Papers
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