PF-05180999 is a phosphodiesterase 2A (PDE2A) inhibitor (IC50 = 1.6 nM).1 It is greater than 2000-fold selective for PDE2A over a panel of ten additional PDEs. PF-05180999 increases striatal, cortical, and hippocampal cGMP levels in mice in a dose-dependent manner. In vivo, it inhibits disruption of low frequency cortical δ oscillation induced by the NMDA antagonist MK-801 in rat brain when administered at a dose of 0.03 mg/kg. PF-05180999 (0.1 and 0.32 mg/kg) inhibits ketamine-induced increases in the number of working memory errors in a radial arm maze task in rats.
1.Helal, C.J., Arnold, E., Boyden, T., et al.Identification of a potent, highly selective, and brain penetrant phosphodiesterase 2A inhibitor clinical candidateJ. Med. Chem.61(3)1001-1018(2018)