Masaru Tanaka 12 Ágnes Szabó 2 István Szatmári 34 Ferenc Fülöp 34 and László Vécsei 12 1 MTASZTE Neuroscience Research Group Semmelweis u 6 H6725 Szeged Hungary ID: 934313
Download Presentation The PPT/PDF document "Antidepressant-like Effects of Kynurenic..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Antidepressant-like Effects of Kynurenic Acid Analogues Masaru Tanaka 1,2, Ágnes Szabó 2, István Szatmári 3,4, Ferenc Fülöp 3,4 and László Vécsei 1,2, *1 MTA-SZTE, Neuroscience Research Group, Semmelweis u. 6, H-6725 Szeged, Hungary; 2 Department of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary; 3 Institute of Pharmaceutical Chemistry and Research Group for Stereochemistry, Hungarian Academy of Sciences, University of Szeged, 6720 Szeged, Hungary;4 Institute of Pharmaceutical Chemistry, Interdisciplinary Excellence Center, University of Szeged, 6720 Szeged, Hungary.* Corresponding author: László Vécsei: vecsei.laszlo@med.u-szeged.hu
1
Slide2Abstract: Kynurenic acid (KYNA) - a metabolite of the L-tryptophan (TRP)-kynurenine (KYN) metabolic pathwayThe intracerebroventricular (i.c.v.) administration of KYNA triggered antidepressant-like effects in modified forced swimming test (FST) of mouseKYNA is impermeable to the blood-brain-barrier (BBB) New KYNA analogues permeable to the BBB in vitroSZR72SZR81SZR104i.c.v. administration of KYNA analogues SZR72: -SZR81: + at least in part through the serotonergic systemSZR104: -
intraperitoneally (
i.p.
) administration of KYNA analogues
SZR72:
-
SZR81: -SZR104: -KYNA analoguesChanged biological propertiesImpermeable to the BBB in vivo ?Peripherally metabolized Keywords: depression; antidepressant; kynurenines; kynurenic acid; analogues;drug design; blood-brain-barrier
2
Slide33IntroductionTryptophan (TRP)-kynurenine (KYN) metabolic pathway> 95% TRP metabolized in the pathwaySynthesize various bioactive moleculesOxidants, antioxidantsNeurotoxins, neuroprotectiveImmunomodulatorsKynurenic acid (KYNA)AntioxidantNeuroprotectiveAntidepressant-likeKYNA impermeable to the blood-brain barrior (BBB)
Slide44Tryptophan (TRP)-Kynurenine (KYN) Metabolic PathwayEncyclopedia. The Tryptophan-Kynurenine Metabolic Pathway. 2021 https://encyclopedia.pub/8633
Slide55Biosysnthesis of Kynurenic acid (KYNA)
Slide66The Blood-Brain-Barrier Permeability of KYN Metabolites Török, N. et al. Int. J. Mol. Sci. 2020, 21, 9338.
Slide77The Effectors of KYNABai, MY. et al. Complex Psychiatry 2021
Slide88Modified forced swim test (FST)Cryan J.F. et al., 1995
Slide99Antidepressant-like Effects of KYNATanaka, Met al. Pharmacol. Rep. 2020, 72, 449–455.
Slide1010The neural pathways of depression
Slide1111Antidepressant-like Effects of KYNA at Least in Part ThroughThe serotonin 5-hydroxytryptamine (5-HT) type 2 receptorsD2, D3, D4 dopamine receptorgamma-aminobutyric acid subunit A receptors
Slide1212Kynurenic Acid and its AnaloguesKynurenic acid Analogues The blood-brain barrier permeable in vitroSZR72SZR81SZR104
Slide1313Antidepressant-like Effects of KYKYNA Analogues (i.c.v.)
Slide1414Antidepressant-like Effects of KYNA Analogues (i.c.v. & i.p.) Antidepressant-like effectsi.c.vi.p.KYNA+-SZR72--
SZR81
+
-
SZR104
-
-
Slide1515ConclusionNovel KYNA analogues may Have lost original biological activities ?Gain new biological activities ?Or may not cross the BBB in vivo ?
Slide1616AcknowledgmentsThe current work was supported by:the Economic Development and Innovation Operational Programme (GINOP) GINOP 2.3.2-15-2016-00034 GINOP 2.3.2-15-2016-00048TUDFO/47138-1/2019-ITM, andTKP2020 Thematic Excellence Programme 2020.