Tallerova A V, Kovalenko L P, Durnev A D, Seredenin S B
Eksp Klin Farmakol. 2011;74(11):3-5.
Effects of the antiasthenic drug ladasten [N-(2-adamantyl)-N-(para-bromophenyl)amine] on the profile of cytokines, behavior, and indexes of immunity organs was studied on zoosocial stress model in depressed C57BL/6 male mice. The anxious depression state in male mice was formed by repeated agonistic interactions according to the sensory contact model. Ladasten (30 mg/kg, i.p.) and reference drug imipramine (10 mg/kg, i.p.) were administered either once after 3-day stressor interaction or for 5 days after 10-day interaction. The concentration of cytokines in blood serum was determined by flow cytometry method. The behavioral changes were studied using an actometer and the elevated plus-maze test. The parameters were studied 24 h after last drug injection. Different stages of depression were manifested by behavioral impairments, increased concentration of pro-inflammatory cytokines IL-6, IL-17, and IL-4, and decreased indexes of immunity organs. Ladasten induced (more significantly than imipramine) a decrease in the level of pro-inflammatory cytokines IL-6, IL-17 and IL-4, removed behavioral changes, and restored indexes of immunity organs. Thus, the antiasthenic drug ladasten limits development of the anxious depressive state and suppresses the level ofproinflammatory cytokines IL-6, IL-17 and IL-4. These findings suggest that ladasten is a possible candidate drug for adjuvant therapy of depressive disorders.
在C57BL/6雄性抑郁小鼠的社会应激模型上，研究了抗疲劳药物拉达司特[N-(2-金刚烷基)-N-(对溴苯基)胺]对细胞因子谱、行为及免疫器官指标的影响。根据感觉接触模型，通过反复的攻击性相互作用在雄性小鼠中形成焦虑抑郁状态。拉达司特（30毫克/千克，腹腔注射）和参比药物丙咪嗪（10毫克/千克，腹腔注射）在3天应激源相互作用后单次给药，或在10天相互作用后连续给药5天。采用流式细胞术测定血清中细胞因子的浓度。使用活动计和高架十字迷宫试验研究行为变化。在最后一次注射药物后24小时研究各项参数。抑郁的不同阶段表现为行为障碍、促炎细胞因子IL-6、IL-17和IL-4浓度升高以及免疫器官指标下降。拉达司特（比丙咪嗪更显著）可降低促炎细胞因子IL-6、IL-17和IL-4的水平，消除行为变化，并恢复免疫器官指标。因此，抗疲劳药物拉达司特可限制焦虑抑郁状态的发展，并抑制促炎细胞因子IL-6、IL-17和IL-4的水平。这些发现表明，拉达司特可能是抑郁症辅助治疗的候选药物。
