New prospects for antipsychotic treatment - the role of the kynurenine pathway
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Kierownik: dr hab. n. med. H. Karakuła-Juchnowicz, Zakład Neuropsychiatrii Klinicznej Katedry i Kliniki Psychiatrii UM w Lublinie
Kierownik: prof. dr hab. n. med. A. Czernikiewicz, Katedra i Klinika Psychiatrii UM w Lublinie
Kierownik: dr. n. med. M. Chrościńska-Krawczyk, Poradnia Zdrowia Psychicznego Dziecięcego Szpitala Klinicznego w Lublinie
Kierownik: Prof. dr hab. n. med. A. Czernikiewicz, Studenckie Koło Naukowe przy Katedrze i Klinice Psychiatrii UM w Lublinie
Kierownik: prof. dr hab. n. med. J. Perzyński, Zakład Pielęgniarstwa Psychiatrycznego UM w Lublinie
Marta Flis   

Kierownik: prof. dr hab. n. med. A. Czernikiewicz, Katedra i Klinika Psychiatrii UM w Lublinie, Ul. Głuska 1, 20-439 Lublin, Polska
Submission date: 2014-01-13
Final revision date: 2014-04-08
Acceptance date: 2014-04-14
Publication date: 2014-12-25
Psychiatr Pol 2014;48(6):1167–1177
The mechanism of action of antipsychotic drugs is mainly associated with changes in dopaminergic system. The application of antipsychotic agents simultaneously produces changes in concentrations of metabolites (e.g. kynurenic acid – KYNA, 3-hydroxykynurenine – 3-OHKYN, kynurenine – KYN) of the kynurenine pathway, the pathway engaged in glutamatergic transmission. The increase in KYNA levels in certain areas of the central nervous system results in inhibition of glutamatergic transmission. Pharmacologically induced elevation of KYNA levels produces effects similar to those observed after administering ketamine or phencyclidine (the noncompetitive NMDA receptor antagonist), concerning increased activity of mesolimbic dopamine neurons, as well as reduction in dopamine release from the prefrontal cortex. Recent research results confirm the predictive value of changes in concentrations of kynurenine pathway metabolites for assessment of effectiveness of antipsychotic treatment. Significant relationships were found 1) in schizophrenia between the reduction of psychopathological symptoms and variations in 3-OHKYN levels as well as changes in KYNA/3-OHKYN and KYN/KYNA ratios, 2) in mania between varying tryptophan concentrations and the reduction in manic symptoms achieved with antipsychotic treatment. The research as well presented the possibilities of kynurenine pathway modifications, raising high hopes for their future application as target points for the action of novel antipsychotic agents.