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首页> 外文期刊>Human psychopharmacology: clinical and experimental >Effects of zotepine and olanzapine on noradrenaline transporter in cultured bovine adrenal medullary cells.
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Effects of zotepine and olanzapine on noradrenaline transporter in cultured bovine adrenal medullary cells.

机译：zotepine和奥氮平的影响去甲肾上腺素转运体在培养的牛肾上腺髓样细胞。

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BACKGROUND: Previously, it was demonstrated that the inhibitory effects of atypical antipsychotic drugs such as clozapine and risperidone on noradrenaline transporter (NAT) might in part be associated with their clinical profile. The present study examined the effects of zotepine on NAT in the cells and compared them with those of olanzapine. MATERIALS AND METHODS: Adrenal medullary cells were isolated by a method of collagenase digestion of slices of fresh bovine adrenal medulla and the cells were plated at a density of 4 x 10(6) cells. Cells were incubated with [(3)H]noradrenaline (NA) in the presence or absence of zotepine or olanzapine. The amount of radioactivity taken into the cells was counted by a liquid scintillation counter. Plasma membranes of bovine adrenal medulla were prepared, and the binding of [(3)H]desipramine (DMI) was determined by incubating the membrane suspension in binding buffer together with zotepine or olanzapine. Specific binding of [(3)H] DMI was defined as that binding which was inhibited by nisoxetine. RESULTS: Both zotepine (10-1000 ng/ml) and olanzapine (10-1000 ng/ml) decreased [(3)H]NA uptake in a concentration-dependent manner. The IC(50) values of zotepine and olanzapine on [(3)H]NA uptake were 10 +/- 4 and 14 +/- 8 ng/ml, respectively. Eadie-Hofstee analysis of [(3)H]NA uptake showed that treatment with zotepine and olanzapine decreased the V(max) of uptake without changing the K(m). Both zotepine (10-1000 ng/ml) and olanzapine (30-1000 ng/ml) inhibited [(3)H]DMI binding in a concentration-dependent manner. The IC(50) values of zotepine and olanzapine on [(3)H]DMI binding were 50 +/- 18, and 120 +/- 38 ng/ml, respectively. Scatchard plot analysis of [(3)H]DMI binding showed that zotepine and olanzapine decreased the B(max) of binding without altering the K(d). CONCLUSIONS: The inhibitory effects of zotepine and olanzapine might be responsible in part for their clinical profile. Copyright (c) 2005 John Wiley & Sons, Ltd.
机译：背景:之前,这是证明非典型抗精神病药物的抑制效应药物如氯氮平、利培酮去甲肾上腺素转运体(NAT)可能在某种程度上与他们相关的临床资料。本研究调查了zotepine的影响NAT的细胞和比较奥氮平。髓细胞被孤立的一个方法胶原酶消化片新鲜的牛肾上腺髓质和细胞被镀的4 x 10(6)细胞的密度。((3) H)与去甲肾上腺素(NA)或存在缺乏zotepine或奥氮平。放射性物质进入细胞数了液体闪烁计数器。牛肾上腺髓质准备,绑定的[(3)H]去郁敏(DMI)确定通过孵化膜悬浮在绑定缓冲连同zotepine或奥氮平。特定的绑定[(3)H] DMI被定义为绑定由nisoxetine抑制。结果:两种zotepine (10 - 1000 ng / ml)奥氮平(10 - 1000 ng / ml)下降[(3)H] NA浓度的方式吸收。IC zotepine和奥氮平(50)值[(3) H] NA吸收10 + / - 4和14 + / - 8 ng / ml,分别。表明zotepine治疗和吸收奥氮平V (max)的摄入没有减少改变K (m)。和奥氮平(30 - 1000 ng / ml)抑制[(3) H] DMI绑定在一个浓度的方式。奥氮平对[(3)H] DMI绑定50 + / - 18日和120 + / - 38 ng / ml,分别。情节的分析[(3)H]表明,DMI绑定zotepine和奥氮平的B (max)有所下降绑定在不改变K (d)。zotepine和奥氮平的抑制效应可能部分负责临床概要文件。有限公司

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