Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic
Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic
复制标题
DOI：
10.1016/j.ejphar.2005.02.051
复制
发表时间：
2005-05-16
影响因子：
5
通讯作者：
Kikuchi, T
中科院分区：
文献类型：
--
作者：
Tadori, Y;Miwa, T;Kikuchi, T
阿立哌唑是第一个临床批准的具有多巴胺 W 受体部分激动剂活性的非典型抗精神病药物。为了评估阿立哌唑的激动剂和拮抗剂特性，我们建立了表达高密度和低密度人多巴胺 D2 受体长亚型和短亚型的中国仓鼠卵巢细胞系，然后将其特性与 7-{3-[4-(2.3-二甲基苯基)哌嗪基]丙氧基，-2(1H)-喹啉酮 (OPC-4392) 进行比较。 S(-)-3-(3-羟基苯基)-N-正丙基哌啶 ((-3-PPP) 和特麦角脲（其他部分激动剂），以毛喉素刺激的 cAMP 积累为指标。在表达高受体密度的细胞中，所有部分激动剂主要表现为激动剂。然而，在表达低受体密度的细胞中，部分激动剂显示出明显低于多巴胺的最大作用，阿立哌唑显示出最低的内在活性，在此外，所有化合物都能阻断多巴胺的作用，其最大效果与每种化合物单独的效果相同，阿立哌唑的低内在活性可能是临床发现的原因：与其他部分激动剂不同，它对精神分裂症的阳性和阴性症状均具有显着的活性，(c) 2005 Elsevier B.V. 保留所有权利。
Aripiprazole is the first clinically approved atypical antipsychotic agent having dopamine W receptor partial agonist activities. To evaluate aripiprazole's agonist and antagonist properties, we established a Chinese hamster ovary cell line expressing high and low densities of the long and short isoforms of human dopamine D2 receptors, then compared its properties with 7-{3- [4-(2.3-dimethylphenyl)piperazinyl]propoxy, -2(1H)-quinolinone (OPC-4392). S(-)-3-(3 -hydroxyphenyl)-N-n-propylpiperidine ((-3-PPP), and terguride (other partial agonists) using forskolin-stimulated cAMP accumulation as an index. In cells expressing high receptor densities, all partial agonists predominantly behaved as agonists. However, in cells expressing low receptor densities, the partial agonists showed significantly lower maximal effects than dopamine, Aripiprazole showed the lowest intrinsic activities, In addition, all compounds blocked the action of dopamine with a maximum effect equal to that of each compound alone, Aripiprazole's low intrinsic activities may account for the clinical finding that, unlike the other partial agonists, it is substantially active against both positive and negative symptoms of schizophrenia, (c) 2005 Elsevier B.V. All rights reserved.