Rolipram

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Chemical compound

title: "Rolipram" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["abandoned-drugs", "pde4-inhibitors", "phenol-ethers", "pyrrolidones", "cyclopentyl-compounds"] description: "Chemical compound" topic_path: "arts/music" source: "https://en.wikipedia.org/wiki/Rolipram" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464383368 | IUPAC_name = (RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one | image = Rolipram.svg | image_class = skin-invert-image | width = 200

| tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_UK = | legal_US = | legal_status = Investigational | routes_of_administration =

| bioavailability = 75% | protein_bound = | metabolism = Liver via CYP2C8, CYP2C9, CYP2C19 and CYP2D6 | elimination_half-life = 3 hours | excretion = Urine (80%)

| IUPHAR_ligand = 5260 | CAS_number_Ref = | CAS_number = 61413-54-5 | ATC_prefix = none | ATC_suffix = | ATC_supplemental = | ChemSpiderID_Ref = | ChemSpiderID = 4913 | ChEBI_Ref = | ChEBI = 104872 | StdInChI_Ref = | StdInChI = 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) | StdInChIKey_Ref = | StdInChIKey = HJORMJIFDVBMOB-UHFFFAOYSA-N | PubChem = 5092 | DrugBank_Ref = | DrugBank = DB04149 | UNII_Ref = | UNII = K676NL63N7 | ChEMBL_Ref = | ChEMBL = 63 | KEGG_Ref = | KEGG = D01783

| C=16 | H=21 | N=1 | O=3 | smiles = COc1ccc(cc1OC1CCCC1)C1CNC(=O)C1

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. Rolipram continues to be used in research as a well-characterized PDE4 inhibitor. Alzheimer's disease, cognitive enhancement, spinal cord injury, and respiratory diseases like asthma and COPD.

References

References

  1. (1990). "Pharmacokinetics of (+)-rolipram and (-)-rolipram in healthy volunteers". European Journal of Clinical Pharmacology.
  2. (Winter 2001). "The antidepressant and antiinflammatory effects of rolipram in the central nervous system". CNS Drug Reviews.
  3. (December 2006). "Cyclic Nucleotide Phosphodiesterases in Health and Disease". CRC Press.
  4. (January 2016). "Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling". Nature Medicine.
  5. (April 2013). "Phosphodiesterase 4-targeted treatments for autoimmune diseases". BMC Medicine.
  6. (November 2012). "Phosphodiesterases as therapeutic targets for Alzheimer's disease". ACS Chemical Neuroscience.
  7. (November 2008). "Neuroenhancement: status quo and perspectives". European Archives of Psychiatry and Clinical Neuroscience.
  8. (February 2008). "The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury". Experimental Neurology.
  9. (2006). "Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD". Current Medicinal Chemistry.

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abandoned-drugspde4-inhibitorsphenol-etherspyrrolidonescyclopentyl-compounds