Sertraline and clomipramine inhibit nucleotide catabolism in rat brain synaptosomes.

Toxicol In Vitro

Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul., Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.

Published: June 2007

AI Article Synopsis

  • Sertraline and clomipramine, two types of antidepressants, were found to inhibit NTPDase activity in rat brain synaptosomes, which are structures that help transmit signals in the brain.
  • Sertraline reduced ATP and ADP hydrolysis significantly in both the cerebral cortex and hippocampus, with varying levels of inhibition based on concentration.
  • Both antidepressants had no effect on AMP hydrolysis, indicating that they may influence ATP levels in the synaptic cleft, potentially altering brain signal modulation.

Article Abstract

The effects of sertraline, a selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant, were tested on ecto-nucleotidases from synaptosomes of cerebral cortex and hippocampus of rats. Sertraline and clomipramine (100-500 microM) inhibited NTPDase, but not ecto-5'-nucleotidase activity in both cerebral cortex and hippocampus. In cortical synaptosomes, sertraline inhibited both ATP and ADP hydrolysis in the concentrations tested. The inhibitory effect varied from 21% to 83% for ATP hydrolysis and 48% to 75% for ADP hydrolysis. The inhibition promoted by sertraline in hippocampal synaptosomes varied from 38% to 89% for ATP hydrolysis and 45% to 77% for ADP hydrolysis. A significant inhibition of cortical NTPDase activity by clomipramine was observed in the all concentrations tested (35-72% and 36-87% for ATP and ADP hydrolysis, respectively). Similar effects were observed in hippocampus (29-91% and 48-83% for ATP and ADP hydrolysis, respectively). There was no inhibitory effect of sertraline and clomipramine on AMP hydrolysis in cerebral cortex and hippocampus. Our results have shown that classical antidepressants inhibit the extracellular catabolism of ATP. Therefore, it is possible to suggest that changes induced by antidepressants on bilayer membrane could affect NTPDase activities and consequently, modulating ATP and adenosine levels in the synaptic cleft.

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http://dx.doi.org/10.1016/j.tiv.2007.01.006DOI Listing

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