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Currently kynurenines are considered a hot topic, because of their involvement in numerous physiological and pathological processes. The essential amino acid, tryptophan's main metabolism is through the kynurenine pathway. During the degradation of tryptophan, kynurenic acid is formed with the help of kynurenine aminotransferases. Kynurenic acid is an excitatory receptor ligand and it possesses neuroprotective properties. Abnormal decrease or increase in the kynurenic acid level can cause an imbalance in the neurotransmitter systems and it is associated with several neurodegenerative and neuropsychiatric disorders. Kynurenic acid has a poor penetration through the blood-brain barrier, so it is unfit for therapeutic purposes. For this reason, the aim of our research was the synthesis and pharmacological testing of kynurenic acid analogues with a better blood-brain barrier penetration. The newly synthetized kynurenic acid analogues proved to be effective in models of some nervous system disorders (migraine, Huntington's disease). According to our results with the novel kynurenic acid analogues, these molecules may represent a new therapeutic target in the treatment of neurodegenerative diseases. Several patent applications were filed based on our results. Orv Hetil. 2020; 161(12): 443-451.

The kynurenine pathway is the main route of tryptophan degradation which gives rise to several neuroactive metabolites. Kynurenic acid is an endogenous antagonist of excitatory receptors, which proved to be neuroprotective in the preclinical settings. Kynurenines have been implicated in the neuroendocrine regulatory processes. Stress induces several alterations in the kynurenine metabolism and this process may contribute to the development of stress-related pathological processes. Irritable bowel disease and gastric ulcer are well-known disorders which are related to psychiatric comorbidity and stress. In experimental conditions kynurenic acid proved to be beneficial by reducing inflammatory processes and normalizing microcirculation in the bowel. Further investigations are needed to better understand the relations of stress and the kynurenines, with the aim of developing novel therapeutic tools for stress-related pathologies.