Lu AF21934 is a brain-penetrant and selective mGlu4 receptor positive allosteric modulator (IC50: 500 nM, human).

mGlu4 (human):500 nM

Lu AF21934的治疗在应激引起的高体温、四板和掩埋大理石测试中表现出剂量依赖性的抗焦虑样效应。在SIH测试中，Lu AF21934（5 mg/kg）的抗高体温效应被苯二氮卓类受体拮抗剂氟马西尼（10 mg/kg）抑制，并且这种效应不依赖于血清素。Lu AF21934在小鼠的尾悬挂测试中不产生抗抑郁样效应；然而，它能降低未适应活动笼的小鼠的基础运动活性。

The receptor-expressing CHO cells are seeded into 24-well plates at a density of 4×104 cells/well and cultured for 1 day. The cells are then incubated with [5,6,8,9,11,12,14,15-3H]arachidonic acid (11 kBq/well) for 1 day and ished with DMEM supplemented with 20 mM HEPES and 0.2% BSA. The cells are then preincubated with the compounds (Sufugolix) at 37 °C for 60 min and the reaction is started by addition of LHRH (1 nM). After incubation at37 °C for 40 min, radioactivity in the medium is measured with a liquid scintillation counter[1].