GABAa-receptors proved to be the molecular targets of ethanol on immune and nervous cells, potentiating alcohol influence. ortho-Fluoro-benzonal is known to be a circular urea derivative and an artificial ligand of GABA/BD-receptor and thus a potential candidate drug for alchoholism treatment.

We have shown the alcohol motivation decrease under ortho-fluoro-benzonal influence in experiment. The investigation of molecular mechanisms and functional targets of this substance is an important step in understanding of molecular pathogenesis and approaches to managing alcohol addiction.

Splenocytes from male (CBAxC57Bl/6) F1 mice in a state of alcohol dependence owing to 6-month 10% ethanol exposure were aseptically obtained and cultured in presence of GABA, ortho-fluoro-benzonal and mitogens (LPS or concanavalin A). Proliferative activity of immune cells in vitro was estimated by means of radioactive 3H-thymidine incorporation.

The intact animals’ splenocytes revealed increased spontaneous proliferation, increased T-mitogen stimulated and decreased B-mitogen stimulated proliferation in the presence of ortho-fluoro-benzonal. The immune cells from alcoholized animals, demonstrating increased spontaneous proliferative activity and weaken susceptibility to the mitogens, showed normal response patterns, except B-mitogen response case, under ortho-fluoro-benzonal inluence. Addition of GABA into the cultures didn’t cancel most positive effects of ortho-fluoro-benzonal inluence, proving existence of their GABAaR-independent pathways, mediated by other barbiturate receptors in addition to GABAaR-dependent ones.

Immunomodulating properties of artificial GABA receptor ligand, ortho-fluoro-benzonal, in vitro has been shown. The compound may correct immune cells dysregulation caused by chronic ethanol exposure, so the original anticonvulsant has promise in the treatment of alcoholism.

The authors have not supplied a conflict-of-interest statement.

Original 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.

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.

(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.

It 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.

Original 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 alcoholism

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