А bstract . Psychoimmunomodulating properties of phenotropil succinate, a new phenotropil derivative, were studied in a model of cyclophosphamide-induced immunodepression and lypopolysaccharideinduced immune stress, following intraperitoneal injections of the drug at different schedules (from a single injection up to a 7-day course), and at varying doses (25 mg/kg, 50 mg/kg, and 100 mg/kg). It was found that the studied substance shows a clear ability to eliminate disorders of various immune compartments. Moreover, phenotropil succinate was able to restore behavioral reactions in “Suоk-test”. These results provide evidence for development of this substance aimed for correction of neuroimmune disturbances. ( Med. Immunol., 2011, vol. 13, N 1, pp 55-60)

The psychoimmunomodulatory properties of phenotropil succinate were studied in conditions of experimental informational-physical stress in Wistar rats. Stress was modeled by alternation of two loads: physical (swimming with a load of 10% of body weight as long as could be tolerated) and informational (formation of a food-procuring behavior in a multiple-choice maze) for 20 days. The effects of phenotropil succinate on the specific and nonspecific resistance of the body were studied. Changes in the animals’ psychoemotional status during exposure to phenotropil succinate were analyzed in the elevated plus maze test and the Porsolt test. The results provide evidence that courses of phenotropil succinate can eliminate neuroimmune impairments developing in conditions of informational-physical stress.

We studied the effect of phenotropil (25 mg/kg intraperitoneally, 5 days) on the immune and psychoemotional state of Wistar rats with LPS-induced immune stress. Hyperactivity of the immune system in animals after treatment with Pseudomonas aeruginosa LPS (100 μg/kg intraperitoneally, 3 days) manifested in a significant increase in the delayed-type hypersensitivity index, antibody titer in the reaction of passive hemagglutination, and phagocytic activity of peripheral blood neutrophils. Locomotor, orientation, and exploratory activities were reduced, while anxiety increased in animals with immune stress. Phenotropil exhibited the psychoimmunomodulatory effect under these conditions, which manifested in prevention of anxiety and fear response, increase in horizontal locomotion and exploratory behavior, and improvement of immunoreactivity.

In Wistar rats, psycho-immune-modulating properties of phenotropyl succinate were studied under conditions of informational-physical stress. The effect ofphenotropyl succinate on the organism specific and unspecific resistance was studied. The data obtained indicate the phenotropyl succinate ability to release neuroimmune disturbances developing under conditions of informational-physical stress.

В обзоре представлены данные о влиянии ГАМК-ергических веществ на функции иммунной системы организма в условиях нормы и патологии. Показано, что активирующее или угнетающее действие ГАМК и ее производных на иммунную систему зависит от фонового состояния организма, а также от вида и величины антигенной нагрузки. Изменение иммунореактивности, полученное через ГАМК-ергическую систему, реализуется при участии дофамин- и серотонинергических механизмов. Иммунотропное действие ГАМК и ГАМК-ергических веществ, очевидно, определяется активирующим влиянием на многоуровневую систему регуляции иммуногенеза, а именно, на ГАМК-чувствительные рецепторы ЦНС и иммунокомпетентных органов, а также гипоталамо-гипофизарно-надпочечникового комплекса.

The review summarizes available data about the influence of GABA-ergic substances on the immune system functional activity under both normal and pathology conditions. Analysis of information in the literature and publications shows that positive/inhibitory effects of GABA and its derivatives on the immune system depend on the overall background organism condition, as well as on parameters such as the level of antigenic stress. In addition, it is shown that changes in the immune reactivity achieved through the GABA-ergic system are dopamine and serotonin dependent. The immunotropic action of GABA and GABA-ergic substances is evidently determined by activating effect upon the multi-level immunogenesis control system, in particular, the GABA-sensitive receptors of the central nervous system and immunocompetent organs, as well as hypothalamo-pituitary-adrenal complex.

There were made experimental studies of immunocorrective RGPU-147 properties upon a single intra-abdominal introduction in the dosage of 36,5; 75 and 146 mg/kg and peroral usage in the dose of 50 mg/kg for two weeks, as well as upon administration to the point of induction of cyclophosphamide immunodepression and in conditions of developing immune insufficiency. The degree of humoral reaction (titer of antierythrocytic antibodies) expression and cellular reaction (the hypersensitivity reaction of slowed-up type index) of immune response. The results showed the ability of RGPU-147 to prevent and to relieve experimentally induced immune disorders upon single and systematic adminsitration.

During the experiment it was found out that use of apple acid of phenotropil may lead not only to refusal of inhibiting action of cyclophosphamide to the formation of cellular and humoral parts of immune reaction.