Effects of Fluoxetine and Norfluoxetine on 5-Hydroxytryptamine Metabolism in Blood Platelets and Brain after Administration to Rats

Abstract

Abstract 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 3h 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 μg g−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.