Nagai Y, Narumi S, Miyamoto M, Shima T, Saji Y, Nagawa Y
Nihon Yakurigaku Zasshi. 1985 Apr;85(4):209-20. doi: 10.1254/fpj.85.209.
The effects of a TRH (thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), on the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and the metabolites in the various brain regions of rats were determined by means of high performance liquid chromatography with electrochemical detection. DN-1417 (20 mg/kg, i.p.) produced marked decreases in the levels of NE, DA and 5-HT, especially in the nucleus accumbens, striatum and hypothalamus. The maximum effect was observed at 15 min after the administration. DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased significantly in the nucleus accumbens, striatum and hypothalamus, whereas 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid remained unchanged. 3-Methoxytyramine increased significantly in the nucleus accumbens and striatum. Two week chronic administration of DN-1417 (20 mg/kg, i.p.) increased the levels of DA and NE in the nucleus accumbens and DA in the striatum. These results suggest that DN-1417 stimulates the turnover of the cerebral monoamines, especially the release of DA from the nucleus accumbens and striatum in the mesolimbic and nigro-striatal DAergic systems.
采用高效液相色谱-电化学检测法，测定促甲状腺激素释放激素（TRH）类似物DN-1417（γ-丁内酯-γ-羰基-L-组氨酰-L-脯氨酰胺柠檬酸盐）对大鼠各脑区去甲肾上腺素（NE）、多巴胺（DA）、5-羟色胺（5-HT）及其代谢产物水平的影响。腹腔注射DN-1417（20mg/kg）可使NE、DA和5-HT水平显著降低，尤其是伏隔核、纹状体和下丘脑。给药后15分钟观察到最大效应。伏隔核、纹状体和下丘脑的DA代谢产物3,4-二羟基苯乙酸和高香草酸显著增加，而3-甲氧基-4-羟基苯乙二醇和5-羟基吲哚乙酸保持不变。伏隔核和纹状体中的3-甲氧基酪胺显著增加。连续两周腹腔注射DN-1417（20mg/kg）可使伏隔核中的DA和NE水平以及纹状体中的DA水平升高。这些结果表明，DN-1417刺激脑单胺的周转，尤其是中脑边缘和黑质纹状体多巴胺能系统中伏隔核和纹状体的DA释放。
