N-正丁基-3-甲氧基喹喔啉-2-甲酰胺（6o）（一种5-羟色胺3受体拮抗剂）的抗抑郁样活性

Anti-depressant like activity of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) a 5-HT3 receptor antagonist.

作者信息

Bhatt Shvetank, Mahesh Radhakrishnan, Devadoss Thangaraj, Jindal Ankur

机构信息

Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333 031, India.

出版信息

Indian J Exp Biol. 2013 Jun;51(6):435-43.

PMID:23926691

Abstract

The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.

摘要

具有最佳脂水分配系数（log P）和亲和力常数（pA2）值的化合物6o（腹腔注射，剂量为0.5、1和2 mg/kg），接受了强迫游泳试验（FST）和悬尾试验（TST）。化合物6o显著缩短了小鼠的不动时间，且不影响其在光电计中的基线运动。此外，6o（腹腔注射，2 mg/kg）增强了5-羟色氨酸（5-HTP）诱导的小鼠头部抽搐反应，并且在腹腔注射1和2 mg/kg时，拮抗了利血平诱导的大鼠体温过低（RIH）。在使用FST与各种标准药物/配体进行的相互作用研究中，6o（腹腔注射，1和2 mg/kg）增强了氟西汀（腹腔注射，5 mg/kg）的抗抑郁作用，并通过缩短不动时间逆转了小白菊内酯（腹腔注射，1 mg/kg）的抑制作用。此外，6o（腹腔注射，1和2 mg/kg）增强了安非他酮（腹腔注射，10 mg/kg）在TST中的作用。从改良旷场试验（参数：行走、站立、粪便颗粒）观察到，慢性给予6o（1和2 mg/kg）会加剧嗅球切除（OBX）大鼠的行为异常。结果表明，化合物6o在啮齿动物抑郁模型中表现出类似抗抑郁的作用。