A-437203 (Lu201640) is A kind of based on 1 h - pyrimidin - 2 - one sca ff old, selective, new powerful d3 receptor antagonist, on D2, d3, and D4 receptor, Ki value 71, respectively 1.6 and 6220 nM.

D4 receptor:6220 nM , D2 receptor:71 nM (Ki), D3 receptor:1.6 nM

A-437203是一种具有高亲和力的D3受体拮抗剂，并相对于其他多巴胺受体亚型具有较高的选择性（与D2相比，对D3的选择性高出44倍）[1]。

A-437203在大鼠强迫游泳测试（FST）中单独测试。A-437203剂量为0.52、1.75、5.24和17.46 μmol/kg，注射方式为静脉注射。剂量的选择基于A-437203对D3与D2多巴胺受体的选择性。17.46 μmol/kg（10 mg/kg）或更低剂量的A-437203效果明显由D3受体介导，而非D2受体。174.6 μmol/kg（100 mg/kg）等高剂量的化合物才能结合并阻断D2受体，避免被烷化剂EEDG不可逆地失活。方差分析（ANOVA）表明，对于分析的任何行为，各处理组之间无显著差异（对于不动行为F4, 45=1.12, p=0.359，对于攀爬行为F4, 45=0.188, p=0.943，对于游泳行为F4, 45=1.634, p=0.182）。基于这些结果，选择17.46 μmol/kg静脉注射剂量的A-437203进行进一步实验[1]。

Male Sprague-Dawley rats weighing 250-350 g are used for these experiments. Haloperidol (0.27, 1.33, and 2.66 μmol/kg=0.1, 0.5, and 1.0 mg/kg i.p.), A-437203 (LU-201640) (0.52, 1.75, 5.24, and 17.46 μmol/kg=0.3, 1.0, 3.0, and 10.0 mg/kg i.p.), and L-745,870 (0.23, 1.15, 2.3, and 5.7 μmol/kg=0.1, 0.5, 1.0, and 2.5 mg/kg i.p.) are tested initially alone in order to determine effective dose ranges. In those experiments, haloperidol, A-437203, and L-745,870 are administered i.p. 24, 5, and 0.5 h before the test swim. In the subsequent antagonism experiments, Haloperidol (0.27 μmol/kg), A-437203 (17.46 μmol/kg) or L-745,870 (1.15 μmol/kg) are injected i.p. 15 min prior to each quinpirole injection (0.4 and 1.0 μmol/kg s.c.).