Plasma and CNS concentrations of Gaboxadol in rats following subcutaneous administration
Plasma and CNS concentrations of Gaboxadol in rats following subcutaneous administration
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DOI：
10.1016/j.ejphar.2007.01.017
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发表时间：
2007-05-07
影响因子：
5
通讯作者：
Ebert, Bjarke
中科院分区：
文献类型：
--
作者：
Cremers, Thomas;Ebert, Bjarke
加波沙朵被认为是一种选择性突触外GABA（A）受体激动剂。然而，几乎没有关于治疗相关剂量下中枢神经系统（CNS）中加波沙朵浓度的信息。为了研究这一点，大鼠皮下注射加波沙朵和血浆和中枢神经系统的浓度进行了测定，使用动态无净流量和超低微透析方法。使用这两种方法的结果相似，表明加波沙朵迅速进入脑，2.5、5和10 mg/kg后的CNS峰浓度在0.7 - 3 μ M范围内。此外，在血浆和CNS中观察到非常短的半衰期（28 min）。可以得出结论，加波沙朵在CNS中的浓度在一定范围内，这可能仅激活突触外（含有非γ亚基）GABAA受体。(c)2007 Elsevier B. V.保留所有权利。
Gaboxadol has been suggested to be a selective extrasynaptic GABA(A) receptor agonist. However, there is little information on Gaboxadol concentrations in the central nervous system (CNS) at therapeutically relevant doses. In order to investigate this, rats were injected subcutaneously with Gaboxadol and plasma and CNS concentrations were determined using the dynamic-no-net-flux and ultraslow microdialysis methods. Results using the 2 methods were similar and showed that Gaboxadol rapidly entered the brain and that peak CNS concentrations after 2.5, 5 and 10 mg/kg were in the range of 0.7 to 3 mu M. Furthermore, a very short half-life (28 min) in both plasma and CNS was observed. It is concluded that concentrations of Gaboxadol in the CNS are in a range, which are likely to activate only extrasynaptic (nongamma subunit containing) GABAA receptors. (c) 2007 Elsevier B.V. All rights reserved.