Raymond S Hurst, Mihaly Hajós, Mario Raggenbass, Theron M Wall, Nicole R Higdon, Judy A Lawson, Karen L Rutherford-Root, Mitchell B Berkenpas, W E Hoffmann, David W Piotrowski, Vincent E Groppi, Geraldine Allaman, Roch Ogier, Sonia Bertrand, Daniel Bertrand, Stephen P Arneric
Several lines of evidence suggest a link between the alpha7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR...
April 27, 2005: Journal of Neuroscience