Journal of Neural Transmission

, Volume 119, Issue 2, pp 109–114 | Cite as

Modifications on the carboxylic function of kynurenic acid

  • Ferenc Fülöp
  • István Szatmári
  • József Toldi
  • László Vécsei
Basic Neurosciences, Genetics and Immunology - Original Article


Pharmacological and histological studies of ten new amides of kynurenic acid revealed that N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride has effective neuroprotective properties. Namely, this molecule is: (1) proved to be an effective inhibitor of excitatory synaptic transmission in the CA1 region of the hippocampus both in in vitro and ex vivo studies, (2) in four vessel occlusion model of transient global forebrain ischaemia, measuring the rate of hippocampal CA1 pyramidal cell loss and preservation of long-term potentiation at Schaffer collateral-CA1 synapses, the neuroprotective potential was represented. N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride administration significantly diminished hippocampal CA1 cell loss and preserved LTP expression.


Neuroprotection Ischaemia KYNA synthesis 


  1. Borza I, Horvath C, Farkas S, Nagy J, Kolok S (2006) Kynurenic acid amide derivatives as NR2B receptor antagonists. WO2006010967Google Scholar
  2. Borza I, Kolok S, Galgoczy K, Gere A, Horvath C, Farkas S, Greiner I, Domany G (2007) Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists. Bioorg Med Chem Lett 17:406–409PubMedCrossRefGoogle Scholar
  3. Drieu K (1986) Preparation and definition of Ginkgo biloba extract. Presse Med 15:1455–1457PubMedGoogle Scholar
  4. Fülöp F, Szatmári I, Vámos E, Zádori D, Toldi J, Vecsei L (2009) Syntheses, transformations and pharmaceutical applications of kynurenic acid derivatives. Curr Med Chem 16:4828–4842PubMedCrossRefGoogle Scholar
  5. Gellért L, Göblös A, Sárközi K, Fuzik J, Kis Z, Farkas T, Szatmári I, Fülöp F, Vecsei L, Toldi J (2011) Neuroprotection with a new kynurenic analogue. Eur J Pharmacol 667:182–187PubMedCrossRefGoogle Scholar
  6. Gigler G, Szenasi G, Simo A, Levay G, Harsing LG Jr, Sas K, Vecsei L, Toldi J (2007) Neuroprotective effect of L-kynurenine sulfate administered before focal cerebral ischemia in mice and global cerebral ischemia in gerbils. Eur J Pharmacol 564:116–122PubMedCrossRefGoogle Scholar
  7. Giles GI, Collins CA, Stone TW, Jacob C (2003) Electrochemical and in vitro evaluation of the redox properties of kynurenine species. Biochem Biophys Res Commun 300:719–724PubMedCrossRefGoogle Scholar
  8. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX (2001) The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci 21:7463–7473PubMedGoogle Scholar
  9. Huse H, Whiteley M (2011) 4-Quinolones: smart phones of the microbial world. Chem Rev 111:152–159PubMedCrossRefGoogle Scholar
  10. Luchowska E, Luchowski P, Sarnowska A, Wielosz M, Turski WA, Urbanska EM (2003) Endogenous level of kynurenic acid and activities of kynurenine aminotransferases following transient global ischemia in the gerbil hippocampus. Pol J Pharmacol 55:443–447PubMedGoogle Scholar
  11. Moroni F (1999) Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur J Pharmacol 375:87–100PubMedCrossRefGoogle Scholar
  12. Nagy K, Plangár I, Gellért L, Demeter I, Farkas T, Kis Z, Marosi M, Zádori D, Klivényi P, Fülöp F, Szatmári I, Vecsei L, Toldi J (2011) Molecular structures and functions: comparative studies of some kynurenic acid analogs. J Neural Transm (under publication)Google Scholar
  13. Nemeth H, Toldi J, Vecsei L (2005) Role of kynurenines in the central and peripheral nervous systems. Curr Neurovasc Res 2:249–260PubMedCrossRefGoogle Scholar
  14. Nemeth H, Toldi J, Vecsei L (2006) Kynurenines. Parkinson’s disease and other neurodegenerative disorders: preclinical and clinical studies. J Neural Transm Suppl 70:285–304PubMedCrossRefGoogle Scholar
  15. Nemeth H, Robotka H, Toldi J, Vecsei L (2007) Kynurenines in the central nervous system: recent developments. Cent Nerv Syst Agents Med Chem 7:45–46CrossRefGoogle Scholar
  16. Prescott C, Weeks AM, Staley KJ, Partin KM (2006) Kynurenic acid has a dual action on AMPA receptor responses. Neurosci Lett 402:108–112PubMedCrossRefGoogle Scholar
  17. Rajda C, Bergquist J, Vecsei L (2007) Kynurenines, redox disturbances and neurodegeneration in multiple sclerosis. J Neural Transm Suppl 72:323–329PubMedCrossRefGoogle Scholar
  18. Robotka H, Toldi J, Vecsei L (2008) L-Kynurenine: metabolism and mechanism of neuroprotection. Future Neurol 3:169–188CrossRefGoogle Scholar
  19. Rozsa E, Robotka H, Vecsei L, Toldi J (2008) The Janus-face kynurenic acid. J Neural Transm 115:1087–1091PubMedCrossRefGoogle Scholar
  20. Sas K, Robotka H, Toldi J, Vecsei L (2007) Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 257:221–239PubMedCrossRefGoogle Scholar
  21. Scharfman HE, Goodman JH (1998) Effects of central and peripheral administration of kynurenic acid on hippocampal evoked responses in vivo and in vitro. Neurosci 86:751–764 Google Scholar
  22. Stone TW (2001) Kynurenic acid antagonists and kynurenine pathway inhibitors. Expert Opin Investig Drugs 10:633–645PubMedCrossRefGoogle Scholar
  23. Turski MP, Turska M, Zgrajka W, Kuc D, Turski WA (2009) Presence of kynurenic acid in food and honeybee products. Amino Acids 36:75–80PubMedCrossRefGoogle Scholar
  24. Turski MP, Turska M, Zgrajka W, Bartnik M, Kocki T, Turski WA (2011) Distribution. Synthesis, and Absorption of Kynurenic Acid in Plants. Planta Med 77:858–864Google Scholar
  25. Wolf H (1974) Studies on tryptophan metabolism in man. Scan J Clin Lab Invest 136S:1–186Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ferenc Fülöp
    • 1
  • István Szatmári
    • 1
  • József Toldi
    • 2
  • László Vécsei
    • 3
  1. 1.Institute of Pharmaceutical Chemistry and Research Group for StereochemistryHungarian Academy of Sciences, University of SzegedSzegedHungary
  2. 2.Department of Physiology, Anatomy and NeuroscienceUniversity of SzegedSzegedHungary
  3. 3.Department of NeurologyUniversity of SzegedSzegedHungary

Personalised recommendations