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].
[1]hutson ph, finger en, magliaro bc, et al. the selective phosphodiesterase 9 (pde9) inhibitor pf-04447943(6-[(3s,4s)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2h-pyran-4-yl)-1,5-dihydro-4h-pyrazolo[3,4-d]pyrimidin-4-one) enhances synaptic plasticity and cognitive function in rodents. neuropharmacology, 2011, 61(4): 665-676.
