Discrepancy of benzodiazepine receptor occupancy between 3H-flumazenil and 125I-iomazenil in intact mouse brain
Discrepancy of benzodiazepine receptor occupancy between 3H-flumazenil and 125I-iomazenil in intact mouse brain
复制标题
完整小鼠脑中 3H-氟马西尼和 125I-碘马西尼之间苯二氮卓受体占据的差异
DOI：
10.1007/s007020050154
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发表时间：
1999
影响因子：
3.3
通讯作者：
O. Inoue
中科院分区：
文献类型：
--
作者：
R. Hosoi;K. Kobayashi;Y. Watanabe;O. Inoue
摘要用~ 3 H-氟马西尼（FMZ）和~（125）I-碘马西尼（IMZ）分别测定了小鼠脑内苯二氮卓类（BZ）受体结合率，为PET和SPECT研究提供了基础数据。在示踪剂注射前40分钟，用不同剂量的氟硝西泮（FNP）预处理小鼠。在示踪剂注射后20 min，通过断头处死小鼠，并通过Goeders和Kuhar（1985）报道的改良方法测定大脑皮质、海马、小脑和桥-髓质中的受体占有率。在研究的所有区域中，用3 H-FMZ测量的FNP的BZ受体结合率显著高于125 I-IMZ。例如，0.1 mg/kg的FNP几乎抑制50%的~ 3 H-FMZ特异性结合，另一方面，几乎没有观察到相同剂量的FNP对~（125）I-IMZ的抑制。在其他类型的苯二氮卓类激动剂、硝甲西泮和三唑仑或反向激动剂乙基-β-咔啉-3-羧酸酯（CCE）中也观察到这种差异。有趣的是，在使用脑匀浆的体外结合研究中，在这两种放射性配体之间观察到几乎相同的竞争性抑制曲线，这强烈表明在完整脑中可能观察到受体结合的差异。这种差异的机制是未知的，虽然这两个放射性配体的不同动力学性质似乎是一个重要因素。
Summary. The in vivo benzodiazepine (BZ) receptor occupancy in mouse brain was measured by employing 3H-flumazenil (FMZ) in comparison with 125I-iomazenil (IMZ), in order to obtain fundamental data for PET and SPECT studies, respectively. Mice were pretreated with various doses of flunitrazepam (FNP) 40 min prior to the tracer injection. At 20 min after the tracer injection, mice were killed by decapitation and receptor occupancy in cerebral cortex, hippocampus, cerebellum and pons-medulla were determined by the modified method reported by Goeders and Kuhar (1985). In all regions studied, BZ receptor occupancy by FNP measured with 3H-FMZ was significantly higher than that of 125I-IMZ. For instance, 0.1 mg/kg of FNP inhibited almost 50% of the specific binding of 3H-FMZ, on the other hand almost no inhibition of 125I-IMZ with the same dose of FNP was seen. This type of discrepancy was also observed in other types of benzodiazepine agonists, nimetazepam and triazolam, or inverse agonist ethyl-β-carboline-3-carboxylate (CCE). It is of interest that in in vitro binding study using brain homogenate, almost the same competitive inhibition curve was observed between these two radioligands, which strongly suggested that discrepancy of receptor occupancy is likely observed in intact brain. The mechanism for such discrepancy is unknown, although the different kinetics properties of these two radioligand seems to be an important factor.
苯二氮卓受体在体内与 [3H]-Ro 15-1788 结合。
影响因子：
6.1
作者：
Goeders,NE;Kuhar,MJ
通讯作者：
Kuhar,MJ
体内苯二氮卓受体占据：与脑浓度和药效作用的相关性。
DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Miller,LG;Greenblatt,DJ;Paul,SM;Shader,RI
通讯作者：
Shader,RI