D159687 is a selective PDE4D inhibitor,had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit.

D159687 induced a transient increase in CREB phosphorylation which peaked at 6 hrs after treatment ( F (3, 20) = 3.731, P = 0.0425). CREB phosphorylation was optimal at 1 μM ( F (3, 20) = 4.194, P = 0.0302).

cAMP concentrations were measured using the enzyme-linked immunosorbent assay.?On the day of treatment, the attached HT-22 cells were washed with warm phosphate buffer saline and then incubated for 10 min with PBS supplemented with various concentrations of D159687 and further for 10 min with 10 nM isoproterenol in the system52.?After incubation, PBS containing the drugs was removed and the plates were let dry roughly before 200 μl HCl (0.1 M) was added to each well to lyse the cells.?Cell lysates were collected into Eppendorf tubes and centrifuged at 800 g for 15 min. Supernatants were collected for immediate assay or stored frozen for assay later using the cAMP complete ELISA kit according to the assay protocol.