Fernández-Novoa L, Alvarez X A, Détolle-Sarbach S, Guez D, Zas R, Polo E, Cacabelos R
Department of Human Physiology, Complutense University Medical School, Madrid, Spain.
Methods Find Exp Clin Pharmacol. 1996 Apr;18(3):197-203.
S-9977-2 is a new molecule with promnesic and antiamnesic properties. In this study, we investigated the effects of i.p. administration of S-9977-2 on histamine (HA) levels in several regions of the rat brain, and also in peripheral areas, using high performance liquid chromatography (HPLC) with fluorometric detection. S-9977-2 (0.025 mg/kg) induced an increase in the content of HA in the anterior hypothalamic region, with a significant effect 30 min after injection (1.77 +/- 0.36 nmol/g vs. 2.43 +/- 0.40 nmol/g; p < 0.01). It did not significantly modify HA levels in the posterior hypothalamic region, hippocampus, fronto-parietal cortex, blood, spleen, or adrenal glands. A clear tendency to increase HA content was observed in the hippocampus (0.16 +/- 0.03 nmol/g vs. 0.39 +/- 0.31 nmol/g, ns) and fronto-parietal cortex (0.55 +/- 0.45 nmol/g vs. 0.70 +/- 0.28 nmol/g; ns). S-9977-2 at doses of 0.005 and 0.125 mg/kg i.p. did not produce any significant change in HA levels in any of the samples tested 30 min after administration. The present results demonstrate that S-9977-2 increases HA levels in the anterior hypothalamus, which is the brain region with the highest content in histaminergic fibers. This fact suggests that the neuronal HA system might be involved directly or indirectly in the pharmacological actions of S-9977-2.
S-9977-2是一种具有改善记忆和抗遗忘特性的新分子。在本研究中，我们采用带荧光检测的高效液相色谱法（HPLC），研究了腹腔注射S-9977-2对大鼠脑内几个区域以及外周区域组胺（HA）水平的影响。S-9977-2（0.025毫克/千克）可使下丘脑前部区域的HA含量增加，注射后30分钟有显著效果（1.77±0.36纳摩尔/克 vs. 2.43±0.40纳摩尔/克；p<0.01）。它对下丘脑后部区域、海马体、额顶叶皮质、血液、脾脏或肾上腺中的HA水平没有显著影响。在海马体（0.16±0.03纳摩尔/克 vs. 0.39±0.31纳摩尔/克，无显著性差异）和额顶叶皮质（0.55±0.45纳摩尔/克 vs. 0.70±0.28纳摩尔/克；无显著性差异）中观察到HA含量有明显增加趋势。腹腔注射剂量为0.005和0.125毫克/千克的S-9977-2在给药30分钟后，所检测的任何样本中的HA水平均未产生任何显著变化。目前的结果表明，S-9977-2可增加下丘脑前部的HA水平，而下丘脑前部是组胺能纤维含量最高的脑区。这一事实表明，神经元HA系统可能直接或间接参与了S-9977-2的药理作用。
