Anxiolytic Effects of Phosphodiesterase-2 Inhibitors Associated with Increased cGMP Signaling

Abstract

Phosphodiesterase (PDE)-

Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease

“…Depending on the family specificity of the PDEI and the chronicity of use, PDEI treatment can either be anxiolytic or anxiogenic (Kurt et al, 2004;Li et al, 2009;Liebenberg et al, 2012;Masood et al, 2009). In the present study, we did not find any effects of chronic PDE2I treatment on anxiety or depressive-like behavior, as measured by the EZM and FST, respectively, neither in WT nor APPswe/PS1dE9 mice at about 8 months of age.…”

Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present)

“…This suggests that PDE2A plays a role in the regulation of intraneuronal cGMP and cAMP levels in brain areas involved in emotion, perception, concentration, learning, memory 26,27 and CNS disorders such as depression 28 and anxiety. 29 Additionally, peripheral inhibition of PDE2A has also been suggested to have antinoniceptive activity, 30 , 31 and to have an effect in the cardiovascular and respiratory systems by preventing platelet aggregation 32 and regulation of the endothelial barrier function respectively. 33,34,35 Moreover, PDE2A inhibition has also been highlighted as a viable approach for antifungal chemotherapy by reducing the virulence factors of Candida albicans.…”

cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action

“…As a result, under many conditions, the hydrolytic rate of PDEs would be less than maximal and increased cellular cGMP would be predicted to increase hydrolytic rate of these PDEs simply as a result of mass action. PDE2 has low affinity for cGMP (K m Ͼ 10 M), which might suggest limited function in the "physiological" range of cGMP levels found in most cells, but its function has been shown to be physiologically relevant in a number of instances (MacFarland et al, 1991;Bender and Beavo, 2006a;Conti and Beavo, 2007;Surapisitchat et al, 2007;Masood et al, 2008Masood et al, , 2009. PDE1, PDE2, PDE3, and PDE5 have been reported to be present in cardiomyocytes although there are still controversies in this area (see below).…”