On the mechanism of imipramine's influence in lowering p-hydroxyphenylglycol concentrations in the brain. The role of tyrosine.
On the mechanism of imipramine's influence in lowering p-hydroxyphenylglycol concentrations in the brain. The role of tyrosine.
复制标题
关于丙咪嗪降低大脑中对羟基苯乙二醇浓度的影响机制。
DOI：
10.1016/0006-2952(88)90557-6
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发表时间：
1988
影响因子：
5.8
通讯作者：
Sedlock,ML
中科院分区：
文献类型：
--
作者：
Edwards,DJ;Sorisio,DA;Sedlock,ML
在10-40 mg/kg的IMI范围内，对大鼠施用丙咪嗪（IMI）4.5小时后显示出以剂量依赖性方式降低章鱼胺代谢物对羟基苯乙二醇（pHPG）的脑浓度。血浆和脑酪氨酸水平的测定表明，IMI产生减少，但与较短的时间过程比消耗在pHPG，最大的减少发生在1.5小时，之前有任何损失的pHPG。酪氨酸和pHPG水平的降低不能用IMI对摄食量的影响来解释，因为即使在禁食24小时的动物中，酪氨酸和pHPG水平也会降低。与仅接受酪氨酸的动物相比，当大鼠在注射200 mg/kg酪氨酸前4.5小时和处死前5.5小时注射IMI时，脑pHPG水平的升高减弱了约50%。这些数据表明，IMI降低脑pHPG的能力可能涉及两种不同的机制：（1）降低脑和血浆酪氨酸浓度，（2）抑制酪氨酸转化为pHPG。目前尚不清楚这些影响是由于IMI本身还是其代谢产物之一，如去甲基丙咪嗪或去二甲基丙咪嗪，其在血浆中的含量等于或大于IMI。
Administration of imipramine (IMI) to rats was shown to lower after 4.5 hr the brain concentration of the octopamine metabolitep-hydroxyphenylglycol (pHPG) in a dose-dependent manner over the range of 10–40 mg/kg of IMI. Assay of plasma and brain levels of tyrosine revealed that IMI produced a reduction in both but with a shorter time-course than for the depletion in pHPG, with the maximal decreases occurring at 1.5 hr, before there was any loss of pHPG. The reductions in tyrosine and pHPG levels could not be explained by an effect of IMI on food intake, since the levels were diminished even in 24-hr fasted animals. When rats were injected with IMI 4.5 hr before 200 mg/kg of tyrosine and 5.5 hr before being killed, the elevation in brain pHPG levels were attenuated by about 50%, as compared to the animals that received tyrosine alone. These data suggest that the ability of IMI to lower brain pHPG probably involves two distinct mechanisms: (1) a lowering of brain and plasma tyrosine concentrations, and (2) an inhibition of the conversion of tyrosine to pHPG. It is unclear whether these effects are due to IMI itself or to one of its metabolites, such as desmethylimipramine or didesmethylimipramine, which were found in the plasma in amounts equal to or greater than IMI.