title: Cytoprotective Effect of Afobazole and Its Main Metabolite M-11.
abstract: Cell damage depending on activity of quinone reductase 2 (MT3 receptor) was simulated in experiments on bone marrow cell suspension and assessed by menadione-induced DNA breaks measured by comet assay. We analyzed the protective effect of afobazole interacting with MT1, MT3, σ1 receptors, and monoamine oxidase A and its main metabolite M11 that specifi cally binds to MT3 receptors. Both compounds reduced the level of menadione-induced DNA damage (afobazole was effective in lower concentrations in comparison with M-11). Conclusion was made on the contribution of MT3 receptors to the protective effect of afobazole, but the observed concentration differences indicate possible contribution of other targets of anxiolytic drug to the protective mechanisms.
authors.affiliation: V. V. Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia, ikadnikov@gmail.com.
authors.forename: I A
authors.initials: IA
authors.lastname: Kadnikov
authors.forename: M V
authors.initials: MV
authors.lastname: Voronin
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D001854:Bone Marrow Cells / Q000187:drug effects*; D002478:Cells, Cultured; D020552:Comet Assay; D053960:DNA Breaks / Q000187:drug effects*; D001728:Dicumarol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D000090023:Metallothionein 3; D051379:Mice; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D009025:Morpholines / Q000378:metabolism / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects; D044094:Receptors, Melatonin / Q000187:drug effects*; D017480:Receptors, sigma / Q000187:drug effects; D024483:Vitamin K 3 / Q000633:toxicity
chemical_list: C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; C558388:2-(2-(3-hydroxymorpholin-4-yl)ethylthio)-5-ethoxybenzimidazole; D014151:Anti-Anxiety Agents; D001562:Benzimidazoles; D000090023:Metallothionein 3; D008996:Monoamine Oxidase Inhibitors; D009025:Morpholines; C000715430:Mt3 protein, mouse; D018696:Neuroprotective Agents; D044122:Receptor, Melatonin, MT1; D044094:Receptors, Melatonin; D017480:Receptors, sigma; D024483:Vitamin K 3; D001728:Dicumarol; D008995:Monoamine Oxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases