Original compound with anticonvulsant activity in the treatment of alcoholism

Abstract

IntroductionOriginal compound ortho-fluorobenzonal, a barbiturate derivative, is shown to reveal strong anticonvulsant activity by means increasing GABA-mediation. Disturbance of GABA(A) -receptors functions play an essential role in both alcoholism and epilepsy pathogenesis.Objectives Taking into account the presence of GABA(A)-receptors on the lymphocytes surface and involvement of immune system in alcoholism pathogenesis, we investigated ortho-fluorobenzonal effects on the immune and nervous systems functional activities in mice with chronic alcohol exposure to find new perspective pharmacological substances in the treatment of alcoholism.Methods(CBAxC57Bl/6) F1 male mice with 6-month 10% ethanol exposure were undergoing intragastric administration of original compound ortho-fluorobenzonal for 10 days. Animal’s alcohol consumption, behavior and immune parameters were estimated.ResultsIt was found that ethanol daily consumption decreased sharply starting from 2 days of ortho-fluorobenzonal administration and led to the cessation of ethanol consumption by the 4 day in mice with chronic alcohol exposure. Pronounced changes in motor and exploratory activities in “open field” test was registered in long-term alcoholized mice after 10- day course ortho-fluorobenzonal administration. The above behavioral changes were recorded against the brain cytokines synthesis modulation. We have shown also the modulation by ortho-fluorobenzonal of immune system functional activity, in particular, significant cellular and humoral immune response stimulation, estimated by the relative number of antibody forming cells and reaction of delayed-type hypersensitivity respectively.ConclusionsOriginal compound ortho-fluorobenzonal has a positive neuroimmunomodulation effect that manifests itself in the correction of iimmune and behavior disorders caused by the chronic ethanol exposure, therefore, this compound is promising in the therapy of alcoholismDisclosureNo significant relationships.

Effects of the original synthetic ligand of benzodiazepine receptors in long-term alcoholized mice

“…ortho-Fluorobenzonal treatment modulated the level of IL-1β, as well as other cytokines (IL-6, TNFα, IFN-γ, IL-10) in some brain regions (hippocampus, frontal cortex, striatum, hypothalamus) in mice with alcohol dependence, what might serve as one of the mechanisms of the demonstrated animal exploratory behavior stimulation. We have previously shown the ortho-fluorobenzonal ability of GABA-R -mediated modulation of spontaneous and mitogen-induced immune cells proliferative activity in mice with experimental alcohol dependence [3][4][5]. We also revealed the stimulation of the humoral and cellular immune response, estimated respectively by the relative number of antibody-producing spleen cells and the intensity of the delayed type hypersensitivity reaction.…”

“…Recently, an alternative pathway of TLR4 activation mediated by GABA-R has been identified, leading to a change in the balance of pro-and antiinflammatory cytokine ligands on neurons, which is involved in the mechanisms of disturbance of higher nervous activity processes in alcoholism [1]. ortho-Fluorobenzonal is a synthetic ligand of the BDR-GABA-R complex, which, as we have previously established, have immunomodulatory properties mediated by lymphocytic GABA-R [3,4]. The purpose of this work was to study the effect of the synthetic ligands of the GABA-R ortho-fluorobenzonal on the functional activity of the nervous and immune systems in experimental alcoholism.…”