DMXB-A is a prototypic selective alpha7 nicotinic receptor agonist that has been tested extensively both preclinically and in Phasel and 2 clinical tests in schizophrenia. This compound is a weak partial agonist with relatively short plasma half-life. It has been shown to enhance various measures of cognition including increases in attention and sensory gating. The purpose of this Core project is to synthesize DMXB-A in sufficient amounts and purity for further clinical and pre-clinical tests. The FDA has stipulated that the synthetic DMXB-A display a chemical purity equivalent to a commercial product made under Good Manufacturing Practice (GMP) standards. This will require most of the requested effort of the synthetic chemist for Year 1 of the project. A second function of this Core will be to measure plasma samples from animals and humans that have been administered DMXB-A to determine its concentration and those of its active metabolites. This will be done according to previously reported HPLC protocols that allow concurrent measurement of parent compound and its 4-OH, 2-OH, and 2,4-Dihydroxy metabolites. These metabolites are potent full agonists and may be involved in the neurobiological response to DMXB-A administration. These data will allow tests of correlation between clinical effect and plasma drug levels. The final function of the Core will be to identify and synthetically provide additional related compounds for clinical tests. Core C provides clinical research support to Project 1 and basic research support to Projects 4, 5, and 6.

Public Health Relevance

New therapeutic strategies for schizophrenia are needed to improve cognitive dysfunction and negative symptoms and to prevent the development of psychosis. The Center investigates a nicotinic acetylcholine receptor as a new therapeutic target. Investigational results are used to design a new drug treatment for schizophrenia and a preventative nutrient intervention during infant development, both of which activate this r(=^r.e^rifnr

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
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Special Emphasis Panel (ZMH1-ERB-F)
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University of Colorado Denver
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Papaleo, Francesco; Yang, Feng; Paterson, Clare et al. (2016) Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model. J Neurosci 36:4859-75
D'Anna-Hernandez, Kimberly L; Garcia, Esmeralda; Coussons-Read, Mary et al. (2016) Sleep Moderates and Mediates the Relationship Between Acculturation and Depressive Symptoms in Pregnant Mexican-American Women. Matern Child Health J 20:422-33
Wu, Wei-Li; Hsiao, Elaine Y; Yan, Zihao et al. (2016) The placental interleukin-6 signaling controls fetal brain development and behavior. Brain Behav Immun :
Chow, Ke-Huan; Yan, Zihao; Wu, Wei-Li (2016) Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C). J Vis Exp :e53643
Tregellas, Jason R; Smucny, Jason; Legget, Kristina T et al. (2015) Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study. Schizophr Res 169:351-4
Smucny, Jason; Olincy, Ann; Eichman, Lindsay S et al. (2015) Neuronal effects of nicotine during auditory selective attention. Psychopharmacology (Berl) 232:2017-28
Javitt, Daniel C; Freedman, Robert (2015) Sensory processing dysfunction in the personal experience and neuronal machinery of schizophrenia. Am J Psychiatry 172:17-31
Lester, Henry A; Lavis, Luke D; Dougherty, Dennis A (2015) Ketamine inside neurons? Am J Psychiatry 172:1064-6
Wilking, Jennifer A; Stitzel, Jerry A (2015) Natural genetic variability of the neuronal nicotinic acetylcholine receptor subunit genes in mice: Consequences and confounds. Neuropharmacology 96:205-12
Hunter, Sharon K; Gillow, Sabreena J; Ross, Randal G (2015) Stability of P50 auditory sensory gating during sleep from infancy to 4 years of age. Brain Cogn 94:4-9

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