Effects of fluoxetine and norfluoxetine on 5-hydroxytryptamine metabolism in blood platelets and brain after administration to rats.
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.
Bourdeaux
R
R
Laboratoire de Biochimie, CHR Metz-Thionville, Thionville, France.
Desor
D
D
Lehr
P R
PR
Younos
C
C
Capolaghi
B
B
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine