Antidepressant-like actions of an AMPA receptor potentiator (LY392098)
Antidepressant-like actions of an AMPA receptor potentiator (LY392098)
复制标题
DOI：
10.1016/s0028-3908(00)00194-5
复制
发表时间：
2001-06-01
影响因子：
4.7
通讯作者：
Skolnick, P
中科院分区：
文献类型：
--
作者：
Li, X;Tizzano, JP;Skolnick, P
LY392098 是一类新型联芳基丙基磺酰胺的成员，可在体外和体内增强 AMPA 受体介导的反应。在这项研究中，LY392098的效果在两种常用于鉴定临床上有用的抗抑郁药的“行为绝望”模型（强迫游泳和悬尾试验）中进行了评估。 LY392098 在大鼠和小鼠的强迫游泳测试中均减少了不动，两个物种的最小有效剂量均为 0.5 mg/kg（腹腔注射）。 LY392098 (0.1-10 mg/kg, i.p.) 不影响大鼠的运动活动。表明该化合物在强迫游泳测试中减少不动的能力与运动兴奋作用无关。 LY392098 还以剂量依赖性方式降低尾部悬吊试验中的不动性，最小有效剂量为 5 mg/kg (i.p)。非竞争性 AMPA 拮抗剂 (LY300168) 在强迫游泳测试中阻断 LY392098 的活性。但不影响丙咪嗪引起的不动减少。因此，AMPA 受体激活似乎是 LY392098 的抗抑郁样作用所必需的。但不是丙咪嗪。这些发现表明联芳基丙基磺酰胺，例如 LY392098。可能代表一类新型的抗抑郁药。 (C) 2001 Elsevier Science Ltd. 保留所有权利。
LY392098 is a member of a novel class of biarylpropylsulfonamides that potentiates AMPA receptor-mediated responses both in vitro and in vivo. In this study, the effects of LY392098 were evaluated in two "behavioral despair" models (the forced swim and tail suspension tests) commonly used to identify clinically useful antidepressants. LY392098 reduced immobility in the forced swim test in both rats and mice, with a minimum effective dose of 0.5 mg/kg (i.p.) in both species. LY392098 (0.1-10 mg/kg, i.p.) did not affect motor activity of rats. indicating that the ability of this compound to reduce immobility in the forced swim test is unrelated to a motor stimulant action. LY392098 also reduced immobility in the tail suspension test in a dose-dependent manner, with a minimum effective dose of 5 mg/kg (i.p). A non-competitive AMPA antagonist (LY300168) blocked the activity of LY392098 in the forced swim test. but did not affect imipramine-induced reductions in immobility. Thus, AMPA receptor activation appears to be required for the antidepressant-like effect of LY392098. but not imipramine. These findings indicate that biarylpropylsulfonamides, exemplified by LY392098. may represent a novel class of antidepressants. (C) 2001 Elsevier Science Ltd. All rights reserved.