Rolipram

Rolipram
Clinical data

ATC code	none
Legal status
Legal status	Investigational
Pharmacokinetic data
Bioavailability	75%
Metabolism	Liver via CYP2C8, CYP2C9, CYP2C19 and CYP2D6
Biological half-life	3 hours
Excretion	Urine (80%)
Identifiers
IUPAC name (RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one
CAS Number	61413-54-5^Y
PubChem (CID)	5092
IUPHAR/BPS	5260
DrugBank	DB04149^N
ChemSpider	4913^Y
UNII	K676NL63N7^Y
KEGG	D01783^N
ChEBI	CHEBI:104872^Y
ChEMBL	CHEMBL63^Y
ECHA InfoCard	100.057.046
Chemical and physical data
Formula	C₁₆H₂₁NO₃
Molar mass	275.347 g/mol
3D model (Jmol)	Interactive image
SMILES COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1
InChI InChI=1S/C16H21NO3/c1-19-14-7-6-11(12-9-16(18)17-10-12)8-15(14)20-13-4-2-3-5-13/h6-8,12-13H,2-5,9-10H2,1H3,(H,17,18)^Y Key:HJORMJIFDVBMOB-UHFFFAOYSA-N^Y
^NY (what is this?)

Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. It served as a prototype molecule for several companies' drug discovery and development efforts. Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects.

Rolipram has several activities that make it a continuing focus for research. The etiology of many neurodegenerative diseases involves misfolded and clumped proteins which accumulate in the brain. Cells have a mechanism to dispose of such proteins called the proteasome. However, in Alzheimer's disease and some other conditions the activity of these proteasomes is impaired leading to a buildup of toxic aggregates. Research in mice suggests that rolipram has the ability to ramp up the activity of proteasomes and reduce the burden of these aggregates. Preliminary evidence suggests that this can improve spatial memory in mice engineered to have aggregate build-up. It continues to be used in research as a well-characterized PDE4 inhibitor. It has been used in studies to understand whether PDE4 inhibition could be useful in autoimmune diseases, Alzheimer's disease, cognitive enhancement, spinal cord injury, and respiratory diseases like asthma and COPD.

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