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Overview
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Background
PF-04447943 is a potent and selective inhibitor of PDE9 [1]. Phosphodiesterase 9 (PDE9) selectively degrades cGMP and limits the cGMP-mediated signal transduction which occurs following glutamate binding to NMDA receptors. PDE9 in cortex and hippocampus of rodents and humans play an important role in memory and learning [1]. PF-04447943 have high affinity with Ki of 2.8, 4.5 and 18 nM for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1- 8 and 10 -11. In cultured hippocampal neurons, PF-04447943 (30-100 nM) significantly increased neurite outgrowth and synapse formation. Also, PF-04447943 (100 nM) significantly facilitated hippocampal slice LTP evoked by a weak tetanic stimulus [1]. In mice model, PF-04447943 (1 mg/kg) significantly reduced the time spent interacting with the female mouse during the second encounter 24 h later compared to the first encounter, which suggested that PF-04447943 enhanced recognition memory. While, PF-04447943 (3 or 10 mg/kg) didn’t change the interaction times for each encounter. These results suggested that PF-04447943 enhanced memory with an inverted U-shaped dose-response efficacy curve [1].
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- Properties
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Overview