CONCLUSION AND IMPLICATIONS: We conclude that UoS12258 is a potent and selective AMPAR modulator exhibiting cognition enhancing properties in several rat behavioural models superior to other molecules which have previously entered clinical evaluation .
SE Ward, P Beswick, N Calcinaghi, LA Dawson, J Gartlon, F Graziani, DN Jones, L Lacroix, MH Selina Mok, B Oliosi, J Pardoe, K Starr, ML Woolley and MH Harries,
British journal of pharmacology , 2017 03
AMPA receptor positive allosteric modulators represent a potential therapeutic strategy to improve cognition in people with schizophrenia. These studies collectively constitute the preclinical pharmacology data package used to build confidence in the pharmacology of this molecule and enable a clinical trial application.[N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro 1H-inden-2-yl]-2-propanesulfonamide] (UoS12258) was profiled in a number of in vitro and in vivo studies to highlight its suitability as a novel therapeutic agent.We demonstrated that UoS12258 is a selective, positive allosteric modulator of the AMPA receptor. At rat native hetero-oligomeric AMPA receptors, UoS12258 displayed a minimum effective concentration of approximately 10 nM in vitro and enhanced AMPA receptor-mediated synaptic transmission at an estimated free brain concentration of approximately 15 nM in vivo. UoS12258 reversed a delay-induced deficit in novel object recognition in rats after both acute and sub-chronic dosing. Sub-chronic dosing reduced the minimum effective dose from 0.3 to 0.03 mg·kg-1 . UoS12258 was also effective at improving performance in two other cognition models, passive avoidance in scopolamine-impaired rats and water maze learning and retention in aged rats. In side-effect profiling studies, UoS12258 did not produce significant changes in the maximal electroshock threshold test at doses below 10 mg·kg-1 .We conclude that UoS12258 is a potent and selective AMPA receptor modulator exhibiting cognition enhancing properties in several rat behavioural models superior to other molecules that have previously entered clinical evaluation.
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its good they are understanding science behind cognitive dysfunction…i am worried when they reach any finding that illustrate cause behind negative symptoms…!!! Any ways thanks for sharing fire monkey…!!!