R. Bourdeaux et al., Effects of fluoxetine and norfluoxetine on 5-hydroxytryptamine metabolism in blood platelets and brain after administration to rats, J PHARM PHA, 50(12), 1998, pp. 1387-1392
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 th
e 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 cont
rol 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 bra
in were similar, 0.36 +/- 0.03 and 0.34 +/- 0.01 mu g g(-1), respectively,
after administration of fluoxetine or norfluoxetine. There was a good corre
lation between plasma and brain levels of fluoxetine (0.962) and norfluoxet
ine (0.957).
The results suggest that fluoxetine and norfluoxetine lead to reduced level
s of 5-HT in platelets and of 5-HIAA in the brain. Like the parent drug, no
rfluoxetine is a potent and selective inhibitor of 5-HT uptake.