Setoguchi M, Takehara S, Sakamori M, Anami K, Maruyama Y
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Nihon Yakurigaku Zasshi. 1987 Jul;90(1):41-9. doi: 10.1254/fpj.90.41.
The effect of Y-8894 (+/-) 2-[[o-(2-thenyl)phenoxy]methyl] morpholine maleate, which has been shown to improve experimentally induced learning and memory deficits, on cerebral monoamine uptake and turnover was studied in the mouse. The following results were obtained: 1) It inhibited in vitro norepinephrine (NE) uptake to the mouse cerebral synaptosomal fractions about 800 and 1250 times more potently than it did those of dopamine (DA) and serotonin (5-HT), respectively. 2) It dose-dependently inhibited in vivo NE uptake, but not DA or 5-HT uptake. 3) It reduced the accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), increased that of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and had no effect on that of the DA metabolite, homovanillic acid (HVA). These effects were compared with those of imipramine, calcium hopantenate (Ca-hopantenate) and dihydroergotoxine. Y-8894 appeared to act by stimulating the noradrenergic receptor, and it acts to a lesser extent by blocking the serotonergic receptor in the brain.
Y - 8894（±）2 - [[邻 - （2 - 噻嗯甲基）苯氧基]甲基]吗啉马来酸盐已被证明可改善实验诱导的学习和记忆缺陷，本研究在小鼠中探讨了其对脑单胺摄取和周转的影响。获得了以下结果：1）在体外，它对小鼠脑突触体组分中去甲肾上腺素（NE）摄取的抑制作用分别比对多巴胺（DA）和5 - 羟色胺（5 - HT）摄取的抑制作用强约800倍和1250倍。2）在体内，它剂量依赖性地抑制NE摄取，但不抑制DA或5 - HT摄取。3）它减少了NE代谢产物3 - 甲氧基 - 4 - 羟基苯乙二醇（MHPG）的积累，增加了5 - HT代谢产物5 - 羟基吲哚乙酸（5 - HIAA）的积累，而对DA代谢产物高香草酸（HVA）的积累没有影响。将这些作用与丙咪嗪、钙泛酸盐（Ca - 泛酸盐）和双氢麦角毒碱的作用进行了比较。Y - 8894似乎通过刺激去甲肾上腺素能受体起作用，并且在较小程度上通过阻断脑中的5 - 羟色胺能受体起作用。
