HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The PPARgamma agonist FMOC-L-leucine protects both mature and immature brain.

Abstract
(N-[9-fluorenylmethoxycarbonyl]-)-L-leucine (FMOC-L-leucine) and rosiglitazone, two ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), were evaluated in mature (adult mice) and immature (pups) brain injury models. In adult magnesium-deficient mice, a model responsive to both neuroprotective and anti-seizure compounds, FMOC-L-leucine, but not rosiglitazone, protected against audiogenic seizures. The protection afforded by FMOC-L-leucine was alleviated by the PPARgamma antagonist GW9662 (1-2 mg/kg) and was induced in 50% animals by 4.8+/-1.2 mg/kg. At this dose, FMOC-L-leucine modified audiogenic seizure phase durations in convulsing mice differently than prototype antiepileptic drugs did. FMOC-L-leucine (up to 100 mg/kg) was inactive in the 6 Hz seizure test, an adult animal model largely responsive to anti-seizure drugs. In a model of neonatal brain injury, FMOC-L-leucine (4 microg/kg) was neuroprotective against cerebral ibotenate toxicity. It reduced significantly the size of lesions in grey but not in white matter, while rosiglitazone (10 microg/kg) was inactive. Taken as a whole, the present data support neuroprotective potentialities of FMOC-L-leucine towards both mature and immature brain. The PPAR-based protection of immature brain is more important as it is known that classic adult brain protectants (GABA(A) activators, N-methyl-D-aspartate and sodium channel blockers) may be toxic for immature brain. The PPARgamma agonist FMOC-L-leucine is likely to be devoid of these classic protective mechanisms because of its inactivity in the 6 Hz seizure test, its activity in the audiogenic test being explained by neuroprotective rather than intrinsic anti-seizure mechanisms. Targeting PPARs might be thus a promising way to protect immature brain.
AuthorsPierre Maurois, Stéphane Rocchi, Nicole Pages, Pierre Bac, James P Stables, Pierre Gressens, Joseph Vamecq
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) 2008 Apr-May Vol. 62 Issue 4 Pg. 259-63 ISSN: 0753-3322 [Print] France
PMID18343627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • (N-(9-fluorenylmethoxycarbonyl)-)-L-leucine
  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Anticonvulsants
  • Neuroprotective Agents
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Ibotenic Acid
  • Leucine
Topics
  • Anilides (pharmacology)
  • Animals
  • Anticonvulsants (pharmacology)
  • Brain (drug effects)
  • Ibotenic Acid (toxicity)
  • Leucine (analogs & derivatives, pharmacology)
  • Mice
  • Neuroprotective Agents (pharmacology)
  • PPAR gamma (agonists)
  • Rosiglitazone
  • Thiazolidinediones (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: