Rolipram

Rolipram

Rolipram
Systematic (IUPAC) name
(RS)-4-(3-cyclopentyloxy-4-methoxy-phenyl)pyrrolidin-2-one
Clinical data
Legal status
  • Investigational
Pharmacokinetic data
Bioavailability 75%[1]
Metabolism Hepatic via CYP2C8, CYP2C9, CYP2C19 and CYP2D6[1]
Biological half-life 3 hours[1]
Excretion Urine (80%)[1]
Identifiers
CAS Registry Number  Y
87714-57-6
ATC code None
PubChem CID:
IUPHAR/BPS
DrugBank  N
ChemSpider  Y
UNII  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C16H21NO3
Molecular mass 275.347 g/mol
 N   

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. ^ a b c d 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.  
  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.  
  3. ^ a b c 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. (Apr 2013). "Phosphodiesterase 4-targeted treatments for autoimmune diseases". BMC Med. 11 (1): 96.  
  5. ^ García-Osta A, et al. (Nov 2012). "Phosphodiesterases as therapeutic targets for Alzheimer's disease". ACS Chem Neurosci 3 (11): 832–44.  
  6. ^ Normann C, Berger M (Nov 2008). "Neuroenhancement: status quo and perspectives". Eur Arch Psychiatry Clin Neurosci 258 (Suppl 5): 110–4.  
  7. ^ Hannila SS, Filbin MT (Feb 2008). "The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury". Exp Neurol 209 (2): 321–32.  
  8. ^ Huang Z, Mancini JA (2006). "Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD". Curr Med Chem. 13 (27): 3253–62.