Baba T, Takeda H, Lee J W, Takada K, Shibuya T
Department of Pharmacology, Tokyo Medical College, Japan.
Nihon Yakurigaku Zasshi. 1995 Mar;105(3):177-85. doi: 10.1254/fpj.105.177.
The effect of fluvoxamine (FLU) on the amine dynamics in serotonergic, noradrenergic or dopaminergic nervous systems in the rat cerebral limbic system was investigated, with reference to the pharmacological characteristics of FLU. Following single oral administration of 30 and/or 60 mg/kg FLU, significant decreases in the 5-hydroxyindole-3-acetic acid (5-HIAA)/serotonin (5-HT) ratios in the amygdala and hippocampus and the 4-hydroxy-3-methoxyphenylglycol (MHPG)/norepinephrine (NE) ratio in the amygdala were produced. FLU at 15 mg/kg, p.o. also caused a significant increase in MHPG/NE ratio in the hippocampus. On the other hand, imipramine (IMI) at 30 mg/kg, p.o. induced significant decreases in 5-HIAA/5-HT ratio in the hippocampus, MHPG/NE ratios in the amygdala and hippocampus, and 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratios in the amygdala, hippocampus and septum. The 5-HIAA/5-HT ratios in the amygdala and hippocampus and the MHPG/NE ratio in the septum were significantly decreased after repeated oral administration of 30 mg/kg FLU twice daily for 14 days, but the MHPG/NE ratio in the amygdala was increased. In the septum, DOPAC/DA ratio was significantly decreased following repeated administration of IMI at 30 mg/kg, p.o. These findings suggest that FLU inhibits 5-HT turnover in the amygdala and hippocampus as a result of the interference with the neuronal re-uptake mechanism for 5-HT. Also, FLU has an effect on NE turnover in the cerebral limbic system, and the effect may appear in connection with a change in the interaction of nervous systems.
参照氟伏沙明（FLU）的药理学特性，研究了其对大鼠大脑边缘系统中血清素能、去甲肾上腺素能或多巴胺能神经系统中胺动力学的影响。单次口服30毫克/千克和/或60毫克/千克FLU后，杏仁核和海马体中的5-羟吲哚-3-乙酸（5-HIAA）/血清素（5-HT）比值以及杏仁核中的4-羟基-3-甲氧基苯乙二醇（MHPG）/去甲肾上腺素（NE）比值显著降低。口服15毫克/千克的FLU也会使海马体中的MHPG/NE比值显著升高。另一方面，口服30毫克/千克的丙咪嗪（IMI）会导致海马体中的5-HIAA/5-HT比值、杏仁核和海马体中的MHPG/NE比值以及杏仁核、海马体和隔区中的3,4-二羟基苯乙酸（DOPAC）/多巴胺（DA）比值显著降低。每天两次重复口服30毫克/千克的FLU，持续14天后，杏仁核和海马体中的5-HIAA/5-HT比值以及隔区中的MHPG/NE比值显著降低，但杏仁核中的MHPG/NE比值升高。在隔区，口服30毫克/千克的IMI后，重复给药会使DOPAC/DA比值显著降低。这些发现表明，FLU通过干扰5-HT的神经元再摄取机制，抑制了杏仁核和海马体中的5-HT周转。此外，FLU对大脑边缘系统中的NE周转有影响，且这种影响可能与神经系统相互作用的变化有关。
