LY404039 (pomaglumetad) is an effective agonist of recombinant human mGlu2(Ki =149 nM)/mGlu3(Ki =92 nM).

mGlu2/3 (rat neurons):88 nM(Ki), mGlu2 (human recombinant):149 nM(Ki), mGlu3 (human recombinant):92 nM(Ki)

LY404039在血浆中展现更高的暴露度和更好的口服生物利用度。该化合物可能对包括焦虑症和精神病在内的神经精神障碍的治疗具有价值。在野生型动物中，LY404039明显逆转了d-安非他明（AMP）诱导的活动量增加、移动距离增加和休息时间减少。10 mg/kg的剂量下，LY404039逆转了苯环利定（PCP）引发的行为。LY404039对PCP和AMP引发的行为激活的抗精神病样效应，在缺乏mGlu2和mGlu2/3但不是mGlu3受体的小鼠中消失。与此相反，氯氮平和利培酮在野生型和缺乏mGlu2/3受体的小鼠中均能抑制PCP引发的行为。此外，LY404039降低了巴甫洛夫自发恢复（PSR）测试中对乙醇的应答行为，并在复发时减少了酒精剥夺效应（ADE）的表达，但在维持条件下不影响对乙醇的应答行为。LY404039抑制了寻求酒精和复发行为的表达，而不改变酒精自我给予行为。此外，LY404039减弱了安非他命和苯环利定引起的高运动状态。LY404039能抑制条件避免反应，并且还能减少大鼠的恐惧增强惊跳和小鼠的掩埋大理石行为。重要的是，LY404039在条件避免任务中不产生镇静效果或运动功能障碍。LY404039还能增加前额叶皮层中多巴胺和血清素的释放/代谢。

Immunoblotting assay of histone acetylation: PANC-1 cells are treated with 2 μg/mL of Scriptaid for 18 h in culture medium. Treated and untreated cells are harvested with trypsin-EDTA, washed with PBS, and resuspended in a protein sample buffer. Protein concentration is determined by BCA protein assay reagents. Fifty μg of proteins from each sample is loaded on a 12% denaturing polyacrylamide gel. Proteins are subsequently transferred to a nylon membrane using MilliblotGraphite Electroblotter I. The nylon membrane is incubated with rabbit antihuman acetyl-lysine antibody, followed by goat antirabbit antibody coupled to horseradish peroxidase, developed with SuperSignal substrates, and detected by film.