部分激动剂抗精神病药物的属性SSR181507,阿立哌唑和bifeprunox多巴胺D2受体:G蛋白激活和催乳素释放。
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Cosi C, Carilla-Durand E, Assie MB, Ormiere, Maraval M, Leduc N, Newman-Tancredi
部分激动剂抗精神病药物的属性SSR181507,阿立哌唑和bifeprunox多巴胺D2受体:G蛋白激活和催乳素释放。
欧元J杂志。2006年3月27日,535 (3):135 - 44。doi: 10.1016 / j.ejphar.2006.01.051。Epub 2006年3月22日。
- PubMed ID
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16554049 (在PubMed]
- 文摘
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多巴胺D2受体拮抗剂引起高泌乳素血症的程度取决于D2受体封锁。我们比较新的抗精神病药物的影响SSR181507 ((3-exo) 8-benzoyl-n - [[(2 s) 7-chloro-2 3-dihydro-1, 4-benzodioxin-1-yl)甲基]8-azabicyclo (3.2.1) octane-3-methanamine monohydrochloride), bifeprunox (DU127090: 1 - (2-Oxo-benzoxazolin-7-yl) 4 - (3-biphenyl) methylpiperazinemesylate)和SLV313 (1 - (2, 3-dihydro-benzo [1,4] dioxin-5-yl) 4 - [5 - (4-fluorophenyl) -pyridin-3-ylmethyl]哌嗪)与阿立哌唑(7 - 4 - [4 - (2,3-dichlorophenyl) 1-piperazinyl] -butyloxy) 3, 4-dihydro-2 (1 H) -quinolinone)、氯氮平、氟哌啶醇对多巴胺D2受体的功能措施活动在体外和体内:[35 s] -GTPgammaS绑定到膜从Sf9昆虫细胞表达人类多巴胺受体D2长(hD2 L)和大鼠的血清泌乳素水平。所有化合物引起了apomorphine-induced G蛋白在hD2 L多巴胺受体激活。拮抗剂阿立哌唑的效能,bifeprunox和SLV313类似于氟哌啶醇(pK (b) = 9.12),而SSR181507(8.16)和氯氮平(7.35)不太有效。氟哌啶醇、SLV313和氯氮平沉默拮抗剂但SSR181507 bifeprunox和阿立哌唑刺激[35 s] -GTPgammaS绑定了17.5%,26.3%和25.6%,分别比100年microM阿朴吗啡(Emax = 100%)。pEC50s: SSR181507 8.08;bifeprunox 8.97;阿立哌唑,8.56。这些影响被raclopride得罪了。口服后体内,药物增加催乳素释放不同的区段。 SLV313 and haloperidol potently (ED50 0.12 and 0.22 mg/kg p.o., respectively) stimulated prolactin release up to 86 and 83 ng/ml. Aripiprazole potently (ED50 0.66 mg/kg p.o.) but partially (32 ng/ml) induced prolactin release. SSR181507 (ED50 4.9 mg/kg p.o.) also partially (23 ng/ml) enhanced prolactin release. Bifeprunox only weakly increased prolactin at high doses (13 ng/ml at 40 mg/kg) and clozapine only affected prolactin at the highest dose tested (41 ng/ml at 40 mg/kg). Prolactin levels of the corresponding vehicle-treated animals were <4.3 ng/ml. These data show that (1) SSR181507, aripiprazole and bifeprunox, but not SLV313, are partial agonists at dopamine hD2 L receptors in vitro; (2) SSR181507, bifeprunox and aripiprazole exhibit reduced prolactin release in vivo compared with drugs that are neutral antagonists at dopamine D2 receptors.