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Ecto-nucleotidase pathway is altered by different treatments with fluoxetine and nortriptyline.

Authors :
Pedrazza EL
Rico EP
Senger MR
Pedrazza L
Zimmermann FF
Sarkis JJ
Bogo MR
Bonan CD
Source :
European journal of pharmacology [Eur J Pharmacol] 2008 Mar 31; Vol. 583 (1), pp. 18-25. Date of Electronic Publication: 2008 Jan 26.
Publication Year :
2008

Abstract

Depression is one of the most disabling diseases and causes a significant burden to both individual and society. Selective serotonin reuptake inhibitors and tricyclic antidepressants, such as fluoxetine and nortriptyline, respectively, are commonly used in treatment for depression. These antidepressants were tested on cerebral cortex and hippocampal synaptosomes after acute and chronic in vivo and in vitro treatments. In chronic treatment, fluoxetine and nortriptyline decreased ATP hydrolysis (17.8% and 16.3%, respectively) in hippocampus. In cerebral cortex, nortriptyline increased ATP (32.3%), ADP (51.8%), and AMP (59.5%) hydrolysis. However, fluoxetine decreased ATP (25.5%) hydrolysis and increased ADP (80.1%) and AMP (33.3%) hydrolysis. Significant activation of ADP hydrolysis was also observed in acute treatment with nortriptyline (49.8%) in cerebral cortex. However, in hippocampus, ATP (24.7%) and ADP (46.1%) hydrolysis were inhibited. Fluoxetine did not alter enzyme activities in acute treatment for both structures. In addition, there were significant changes in NTPDase activities when fluoxetine and nortriptyline (100, 250, and 500 microM) were tested in vitro. There was no inhibitory effect of fluoxetine and nortriptyline on AMP hydrolysis in cerebral cortex and hippocampus. The findings showed that these antidepressant drugs can affect the ecto-nucleotidase pathway, suggesting that the extracellular adenosine levels could be modulated by these drugs.

Details

Language :
English
ISSN :
0014-2999
Volume :
583
Issue :
1
Database :
MEDLINE
Journal :
European journal of pharmacology
Publication Type :
Academic Journal
Accession number :
18280468
Full Text :
https://doi.org/10.1016/j.ejphar.2008.01.013