Modifications on the carboxylic function of kynurenic acid
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.
KeywordsNeuroprotection Ischaemia KYNA synthesis
- Borza I, Horvath C, Farkas S, Nagy J, Kolok S (2006) Kynurenic acid amide derivatives as NR2B receptor antagonists. WO2006010967Google Scholar
- 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
- 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
- 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
- Wolf H (1974) Studies on tryptophan metabolism in man. Scan J Clin Lab Invest 136S:1–186Google Scholar