Bourdeaux R, Desor D, Lehr P R, Younos C, Capolaghi B
Laboratoire de Biochimie, CHR Metz-Thionville, Thionville, France.
J Pharm Pharmacol. 1998 Dec;50(12):1387-92. doi: 10.1111/j.2042-7158.1998.tb03364.x.
The effects of intraperitoneal administration of fluoxetine (2.5, 5, 10 or 20 mg kg(-1)) and norfluoxetine (10 mg kg(-1)) on 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) metabolism were examined in the blood platelets and brain of rats killed 3 h after a single dose. Several experiments were performed to evaluate the effect of norfluoxetine. Plasma 5-HT concentrations decreased significantly (48%) compared with control group results 3 h after administration of a single dose of fluoxetine (10 or 20 mg kg(-1)). Similar plasma 5-HT levels, 0.54+/-0.04 and 0.56+/-0.09 mg L(-1), respectively, were observed after administration of 10 mg kg(-1) fluoxetine or norfluoxetine. In the same way 5-HIAA levels in whole brain were similar, 0.36+/-0.03 and 0.34+/-0.01 microg(-1), respectively, after administration of fluoxetine or norfluoxetine. There was a good correlation between plasma and brain levels of fluoxetine (0.962) and norfluoxetine (0.957). The results suggest that fluoxetine and norfluoxetine lead to reduced levels of 5-HT in platelets and of 5-HIAA in the brain. Like the parent drug, norfluoxetine is a potent and selective inhibitor of 5-HT uptake.
单次给药3小时后，处死大鼠，检测腹腔注射氟西汀（2.5、5、10或20 mg kg⁻¹）和去甲氟西汀（10 mg kg⁻¹）对血小板和脑中5-羟色胺（5-HT）及5-羟吲哚-3-乙酸（5-HIAA）代谢的影响。进行了多项实验以评估去甲氟西汀的作用。与对照组结果相比，单次注射氟西汀（10或20 mg kg⁻¹）3小时后，血浆5-HT浓度显著降低（48%）。注射10 mg kg⁻¹氟西汀或去甲氟西汀后，观察到相似的血浆5-HT水平，分别为0.54±0.04和0.56±0.09 mg L⁻¹。同样，注射氟西汀或去甲氟西汀后，全脑5-HIAA水平相似，分别为0.36±0.03和0.34±0.01 μg⁻¹。氟西汀和去甲氟西汀的血浆与脑内水平之间存在良好的相关性（分别为0.962和0.957）。结果表明，氟西汀和去甲氟西汀可导致血小板中5-HT水平及脑中5-HIAA水平降低。与母体药物一样，去甲氟西汀是一种强效且选择性的5-HT摄取抑制剂。
