S- (+)-Rolipram

2 years -20°C Powder, 2 weeks 4°C in DMSO, 2 months -80°C in DMSO

Administered via i.v.

Rolipram (including both R- and S-enantiomers of Rolipram) is under the Phase I clinical trial for its antidepressant effects on cAMP specific phosphodiesterase (PDE4) in depressed patients.

S-(+)-Rolipram is dissolved in 100% PEG at an appropriate concentration.

S-(+)-Rolipram suppresses LPS-induced TNFalpha expression from human monocyte through inhibiting PDE4 with IC50 about 2 uM. [1] 1 uM S-(+)-Rolipram significantly antagonizes ovalbumin (OA) induced concentration-related contractions of tracheal rings which are isolated from OA-sensitized guinea pigs. [2] S-(+)-Rolipram inhibits PDE4 activity in a CHO-K1 cell line which stably expresses a recombinant full length human PDE-4a with IC50 at 450 nM. [3] Treatment of the human glioma cell line A-172 with Rolipram (including both R- and S-enantiomers of Rolipram) results in increased expression of the cell cycle inhibitors p21 [Cip1] and p27 [Kip1], and decreased activity of cdk2, a cyclindependent kinase essential for cell cycle progression. As a result, the proliferation of A-172 cells is inhibited, with induction of a G1 block. Eventually, Rolipram-treated A-172 cells undergo differentiation, which is followed by apoptotic cell death. [4]

PDE Assay, PDE activity is determined by the two-step radioisotope method of Thompson et al (1979). The reaction mixture contains: Tris-HCl 20 mM (pH 8.0), MgCl2 10 mM, 2-mercaptoethanol 4 mM, ethyleneglycol-bis-(f-aminoethyl ether) N, N, N', N'-tetraacetic acid (EGTA) 0.2 mM, bovine serum albumin, 0.05 mg/mL. Unless otherwise stated, the substrate concentration is 1 uM. The IC50 values (concentration which produced 50% inhibition of substrate hydrolysis) for the compounds are determined from concentration (0.1 nM to 40 uM)-response curves. At least three concentration-response curves are generated for each agent.

S-(+)-Rolipram inhibits human monocyte cyclic AMP-specific PDE4 with IC50 of 0.75 uM.