title: Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse.
abstract: Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund's adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay. SzV-1287 significantly inhibited hyperalgesia and oedema in both models. Plasma leakage and keratinocyte chemoattractant production in the tibiotarsal joint, but not myeloperoxidase activity was significantly reduced by SzV-1287 in K/BxN-arthritis. SzV-1287 did not influence vascular and cellular mechanisms in CFA-arthritis, but significantly decreased histopathological alterations. There was no difference in the anti-hyperalgesic and anti-inflammatory actions of SzV-1287 and LJP-1207, but only SzV-1287 decreased CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which was confirmed in vitro. SzV-1287 exerts potent analgesic and anti-inflammatory actions in chronic arthritis models of distinct mechanisms, without inducing cartilage damage.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Horváth
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
authors.forename: Awt
authors.initials: A
authors.lastname: Menghis
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Botz
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Borbély
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.|Department of Medical Biology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kemény
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.
authors.forename: Valéria
authors.initials: V
authors.lastname: Tékus
authors.affiliation: Department of Physiology &MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
authors.forename: Janka Zsófia
authors.initials: JZ
authors.lastname: Csepregi
authors.affiliation: Department of Physiology &MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Mócsai
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical School, University of Debrecen, Debrecen, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Juhász
authors.affiliation: Department of Anatomy, Histology and Embryology, Medical School, University of Debrecen, Debrecen, Hungary.
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacology, Semmelweis University, Budapest, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Bogdán
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacology, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Mátyus
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
authors.forename: Julie
authors.initials: J
authors.lastname: Keeble
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.|PharmInVivo Ltd., Pécs, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School; János Szentágothai Research Centre &Centre for Neuroscience, University of Pécs, Pécs, Hungary.|PharmInVivo Ltd., Pécs, Hungary.|MTA-PTE NAP B Chronic Pain Research Group, Pécs, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy*; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005620:Freund's Adjuvant / Q000276:immunology; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010080:Oxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C000613315:3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime; D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D006834:Hydrazines; C506836:N'-(2-phenylallyl)hydrazine; D010080:Oxazoles; D010091:Oximes; D005620:Freund's Adjuvant; D006631:Amine Oxidase (Copper-Containing)