Rolipram

Rolipram
Systematic (IUPAC) name
(RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one
Clinical data
  • Investigational
Pharmacokinetic data
Bioavailability 75%[1]
Metabolism Hepatic via CYP2C8, CYP2C9, CYP2C19 and CYP2D6[1]
Half-life 3 hours[1]
Excretion Urine (80%)[1]
Identifiers
61413-54-5 Yes
87714-57-6
None
PubChem CID 5092
DrugBank DB04149 
ChemSpider 4913 Yes
UNII K676NL63N7 Yes
ChEBI CHEBI:104872 Yes
ChEMBL CHEMBL63 Yes
Chemical data
Formula C16H21NO3
275.347 g/mol
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Rolipram was a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s.[2] It served as a prototype molecule for several companies' drug discovery and development efforts.[3]:668ff 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.[3]:668

It continues to be used in research as a well-characterized PDE4 inhibitor.[3]:669 It has been used in studies to understand whether PDE4 inhibition could be useful in autoimmune diseases,[4] Alzheimer's disease,[5] cognitive enhancement,[6] spinal cord injury,[7] and respiratory diseases like asthma and COPD.[8]

References

  1. ↑ 1.0 1.1 1.2 1.3 Krause, W; Kühne, G; Sauerbrey, N (1990). "Pharmacokinetics of (+)-rolipram and (−)-rolipram in healthy volunteers" (PDF). European Journal of Clinical Pharmacology 38 (1): 71–75. doi:10.1007/BF00314807. PMID 2328751.
  2. ↑ Zhu, J; Mix, E; Winblad, B (Winter 2001). "The antidepressant and antiinflammatory effects of rolipram in the central nervous system.". CNS Drug Reviews 7 (4): 387–98. doi:10.1111/j.1527-3458.2001.tb00206.x. PMID 11830756.
  3. ↑ 3.0 3.1 3.2 McKenna, JM and Muller, GW. Medicinal Chemistry of PDE4 Inhibitors. Chapter 33 in Cyclic Nucleotide Phosphodiesterases in Health and Disease, Eds Joseph A. Beavo et al. CRC Press, Dec 5, 2006 ISBN 9781420020847
  4. ↑ Kumar N et al. Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med. 2013 Apr 4;11:96. doi: 10.1186/1741-7015-11-96. PMID 23557064 PMC 3616808
  5. ↑ García-Osta A et al. Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem Neurosci. 2012 Nov 21;3(11):832-44. PMID 23173065 PMC 3503343
  6. ↑ Normann C and Berger M. Neuroenhancement: status quo and perspectives. Eur Arch Psychiatry Clin Neurosci. 2008 Nov;258 Suppl 5:110-4. PMID 18985306
  7. ↑ Hannila SS and Filbin MT. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol. 2008 Feb;209(2):321-32. PMID 17720160 PMC 2692909
  8. ↑ Huang Z and Mancini JA. Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD. Curr Med Chem. 2006;13(27):3253-62. PMID 17168849