ROLIPRAM

Description

Rolipram (61413-54-5) is a selective inhibitor of cAMP-specific phosphodiesterase (PDE4), IC50 = 1 μM. Displays beneficial effects in neurodegenerative diseases. Rolipram also displays anti-inflammatory activity and synergizes with forskolin (cat.# 10-2073). Cell permeable.

Description

Rolipram, a selective phosphodiesterase-4 inhibitor, was originally developed by Schering as an antidepressant in the 1990s. Although it was a prototype for some drugs developed later, Schering abandoned it because its effective dosage caused significant adverse side effects.
But rolipram isn’t without merit. It was soon discovered that it can accelerate proteasomes’ activity for disposing of toxic protein aggregates that lead to neurodegenerative diseases.
The misfolded tau protein is the aggregate associated with Alzheimer’s disease. Recently, studies by Natura Myeku and co-workers at Columbia University (New York) showed that tau may responsible for attacking proteasomes and disrupting their activity. They then found that when rolipram is administered to mice that were engineered to generate a tau protein, the drug?increases proteasome activity, depresses aggregate formation, and improves the animals’ spatial memory.

Chemical properties

Yellowish solid

The Uses of ROLIPRAM

(±)-Rolipram is a cAMP-specific phosphodiesterase 4 (PDE4) inhibitor.

The Uses of ROLIPRAM

antipsychotic

The Uses of ROLIPRAM

A selective, cell permeable inhibitor of cAMP-specific phosphodiesterase (PDE4).

The Uses of ROLIPRAM

Pharmacological tool for characterization of phosphodiesterase isoenzymes.

What are the applications of Application

Rolipram is a selective, cell permeable inhibitor of cAMP-specific phosphodiesterase (PDE4)

Definition

ChEBI: Rolipram is a member of the lclass of pyrrolidin-2-ones that is pyrrolidin-2-one bearing a 3-(cyclopentyloxy)-4-methoxyphenyl substituent at the 4-position. It is a type IV-specific phosphodiesterase (PDE4) inhibitor. It has a role as an antidepressant and an EC 3.1.4.* (phosphoric diester hydrolase) inhibitor.

General Description

A cell-permeable, selective inhibitor of cAMP-specific phosphodiesterase (PDE IV; IC₅₀ = 800 nM). A rolipram-insensitive PDE IV subtype is also known to exist. Also inhibits NF-κB and NFAT activation in Jurkat and primary T cells.

Biological Activity

Selective inhibitor of cAMP phosphodiesterase (PDE4) (IC 50 = 2.0 μ M). Discriminates between two conformational states of PDE4 isoenzymes. See separate isomers ((R)-(-)-Rolipram and (S)-(+)-Rolipram).

Biochem/physiol Actions

Cell permeable: yes

storage

Room temperature

References

1) Reeves et al. (1987), The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea-pig cardiac ventricle. Implications for the mechanism of action of selective phosphodiesterase; Biochem. J., 241 535 2) Nishi et al. (2008), Distinct Roles of PDE4 and PDE10A in the Regulation of cAMP/PKA Signaling in the Striatum; J. Neurosci., 28 10460 3) Christiansen et al. (2011), Combined anti-inflammatory effects of β2-adrenergic agonists and PDE4 inhibitors on astrocytes by upregulation of intracellular cAMP; Neurochem. Int., 59 837