BACKGROUND 5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and pA2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. METHODS LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. RESULTS The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS-induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. CONCLUSIONS Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain.

中文翻译：

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新型5-HT3受体拮抗剂（4-苄基哌嗪-1-基）（3-甲氧基喹喔啉-2-基）甲酮（6g）对小鼠脂多糖诱发的焦虑模型的神经药理学评估。

背景技术5-HT 3受体拮抗剂在精神疾病如抑郁症和焦虑症的治疗中起关键作用。它们可以通过调节血清素能传递来起作用。在本研究中，一种新型且潜在的5-HT3受体拮抗剂6g（4-苄基哌嗪-1-基）（3-甲氧基喹喔啉-2-基）甲酮，其log P（3.08）和pA2（7.5）值均良好筛选其在脂多糖（LPS）诱导的焦虑模型中的抗焦虑特性。方法革兰氏阴性细菌细胞壁中存在的内毒素LPS被单次注射0.83 mg / kg腹腔注射，以诱发小鼠的焦虑样症状。将化合物6g（1和2 mg / kg，口服）和标准氟西汀（FLX）（20 mg / kg，口服）注入治疗组7天，并在多种行为模式下进行评估，例如高架迷宫（EPM），明暗测试（L / D）和野外测试（OFT）。还检查了它们对小鼠脑中5-羟色胺水平的影响。结果结果表明，LPS在小鼠中诱发了焦虑样症状，其表现为EPM中张开双臂进入的百分比和张开双臂所花费的时间显着减少。在L / D测试中减少了在照明区域上花费的时间以及减少了腔室之间的转换数量；降低了OFT的步行和饲养分数。化合物6g（1和2 mg / kg，口服，共7天）和FLX处理（20 mg / kg，口服，共7天）逆转了LPS诱导的行为变化，并显着影响了上述所有行为参数。另外，6g（1和2 mg / kg，口服，7天）和FLX处理（20 mg / kg，口服，7天）增加了小鼠大脑中5-羟色胺的水平。