Benvenga M J, Leander J D
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Eur J Pharmacol. 1993 Aug 3;239(1-3):249-52. doi: 10.1016/0014-2999(93)91005-8.
The novel 5-HT1A receptor agonist, LY228729, was tested to see if it would produce antidepressant-like behavioural effects in the rodent forced swim model. The tricyclic antidepressant, imipramine, as well as the 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone, produced dose-related decreases in immobility in the forced swim test following subchronic treatment in rats. LY228729, when given over a three injection course, as with the other compounds, significantly reduced immobility at doses of 1 and 3 mg/kg. Subsequent analysis of locomotor activity revealed no increases in behavior, so that general changes in activity could not account for the reduction in immobility time in the forced swim. These results suggest that LY228729 may have clinical antidepressant efficacy.
新型5-羟色胺1A受体激动剂LY228729在啮齿动物强迫游泳模型中进行了测试，以观察其是否会产生类抗抑郁行为效应。三环类抗抑郁药丙咪嗪以及5-羟色胺1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）和吉哌隆，在大鼠亚慢性治疗后的强迫游泳试验中，均产生了与剂量相关的不动时间减少。与其他化合物一样，LY228729在连续注射三次的过程中，在1和3mg/kg的剂量下显著减少了不动时间。随后对运动活性的分析显示行为没有增加，因此一般的活性变化不能解释强迫游泳中不动时间的减少。这些结果表明LY228729可能具有临床抗抑郁疗效。
