Rolipram (SB 95952) is a phosphodiesterase 4 inhibitor with antidepressant properties.

PDE4D:240 nM, PDE4B:130 nM

PDE4选择性抑制剂Rolipram对免疫纯化的PDE4B和PDE4D活性具有相似的抑制作用，其IC50分别约为130 nM和240 nM。相比之下，Rolipram对免疫纯化的PDE4A活性的抑制作用显著更强，IC50约为3 nM。Rolipram还能在剂量依赖性方式中增加U937细胞中cAMP响应元件结合蛋白（CREB）的磷酸化，呈现出高亲和力（IC50约1 nM）和低亲和力（IC50约120 nM）成分。Rolipram剂量依赖性地抑制IFN-γ刺激的p38 MAPK磷酸化，以单调方式进行，IC50约为290 nM。作为一种选择性PDE4抑制剂，Rolipram能够抑制所有的PDE4亚型A、B、C和D。Rolipram还能够剂量依赖性地抑制LPS诱导的J774细胞中TNF产生（IC50 25.9 nM），并且在2 μM化合物浓度下观察到最大/次最大抑制效果。

LPS在野生型（WT）小鼠的腹膜巨噬细胞（PM）中诱导TNF mRNA和蛋白表达，而Rolipram明显抑制了TNF mRNA和TNF蛋白的表达（分别降低了74%和63%）。与WT小鼠的PM相比，MKP-1(-/-)小鼠的PM中LPS诱导的TNF产生增强.Rolipram对MKP-1(-/-)小鼠的PM中TNF mRNA和蛋白表达的抑制明显减弱，且没有达到统计学意义[2]。重复给予Rolipram（1.25 mg/kg, i.p.）能减少学习无助大鼠的逃跑失败次数[3]。

Rolipram is dissolved in DMSO and stored, and then diluted with appropriate medium before use[2]. J774 murine macrophages (ATCC) are cultured at 37°C in 5% CO2 atmosphere in DMEM supplemented with glutamax-1 containing 10% heat-inactivated FBS, 100 U/mL penicillin, 100 μg/mL streptomycin and 250 ng/mL amphotericin B. For experiments, cells are seeded on 24-well plates at a density of 2×105 cells per well. Cell monolayers are grown for 72 h before the experiments are started. Rolipram, IBMX and BIRB 796 are dissolved in DMSO, and 8-Br-cAMP in HBSS. LPS (10 ng/mL) or the compounds of interest at concentrations indicated or the solvent (DMSO, 0.1% v/v) are added to the cells in fresh culture medium containing 10% FBS and the supplements. Cells are further incubated for the time indicated. The effect of LPS and the tested chemicals on cell viability is evaluated by Cell Proliferation Kit II (XTT)[2].