在体外和体内对单胺受体结合,影响营业额在老鼠大脑区域的新型抗精神病药物利培酮和ocaperidone。

文章的细节

引用

复制到剪贴板

莱森我,詹森点,Gommeren W, Wynants J, Pauwels PJ,詹森

在体外和体内对单胺受体结合,影响营业额在老鼠大脑区域的新型抗精神病药物利培酮和ocaperidone。

摩尔杂志。1992年3月,41 (3):494 - 508。

PubMed ID

1372084 (在PubMed

]

文摘

利培酮和ocaperidone新benzisoxazol抗精神病药物特别是精神分裂症的有利影响。我们报告一个全面研究在体外和体内受体结合的新化合物,与氟哌啶醇相比,药物对单胺和代谢物水平的影响在不同的大脑区域。体外受体结合和单胺吸收抑制概要,包括29受体和四个单胺吸收系统,显示ocaperidone和利培酮为主,和亲和力迄今为止最高的报道,血清素5 ht2受体(Ki值分别为0.14和0.12 nM)。此外,绑定在摩尔浓度以下药物受体(Ki值,在海里,ocaperidone和利培酮,分别):α1-adrenergic(0.46和0.81),多巴胺D2(0.75和3.0),组胺H1(1.6和2.1),和α2-adrenergic(5.4和7.3)。相比之下,氟哌啶醇显示摩尔亲和力D2受体(1.55)和haloperidol-sensitiveσ网站(0.84)。ocaperidone的体外亲和力、利培酮和氟哌啶醇D2受体时完全相同的测量从大鼠纹状体膜,伏隔核、嗅结节,和人类肾脏细胞表达克隆人类D2受体(长形式)。在老鼠体内绑定,使用静脉注射[3 h] spiperone管理,显示非常有效的占领ocaperidone和利培酮5 ht2受体的额叶皮质(ED50 0.04 -0.03毫克/公斤);在这方面,他们6 30比ritanserin和强100倍,氟哌啶醇、氯氮平,分别。Ocaperidone占领D2受体在纹状体和伏隔核具有类似效力和氟哌啶醇(ED50 0.14 - -0.16毫克/公斤)。利培酮揭示两相的抑制曲线在后者的大脑区域,表明[3 h] spiperone标签都5 ht2受体(被利培酮在小于0.04毫克/公斤)和D2受体(利培酮ED50约1毫克/公斤)。 In the tuberculum olfactorium, 5HT2 and D2 receptors were also distinguished with risperidone. The ED50 values for occupation of the latter were for ocaperidone and risperidone 2 times lower and for haloperidol 2 times higher than in the striatum. Ocaperidone, risperidone, and haloperidol readily increased the levels of the dopamine metabolites 3,4-dihydroxybenzene acetic acid and homovanillic acid in the striatum, the nucleus accumbens, the tuberculum olfactorium, and, to some extent, the frontal cortex. Dose-response curve shapes were markedly different; with ocaperidone maximal levels were reached at 0.16 mg/kg and maintained to 10 mg/kg; with risperidone the levels tended to increase continuously up to 10 mg/kg. Haloperidol produced dome-shaped curves (maximum at 0.16-0.63 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS)

beplay体育安全吗DrugBank数据引用了这篇文章

药物

Ocaperidone