Sertraline reduces glutamate uptake in human platelets

• Published in: Neurotoxicology (Park Forest South) Vol. 51; pp. 192 - 197
• Main Authors: Rodrigues, Débora Olmedo, Bristot, Ivi Juliana, Klamt, Fábio, Frizzo, Marcos Emílio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2015
• Subjects: Adenosine Triphosphate - blood; Adenosine Triphosphate - metabolism; Blood Platelets - metabolism; Cell Survival - drug effects; Excitotoxicity; Glutamic Acid - metabolism; Glycogen - blood; Glycogen - metabolism; Humans; Lithium; Male; Seizures; Serotonin Uptake Inhibitors - toxicity; Sertraline - toxicity; SSRI; SSRI; Lithium; Excitotoxicity; Seizures
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2015.10.014

•Cell viability and ATP levels are not affected by sertraline at therapeutic levels.•Sertraline in the low micromolar range decreases glutamate uptake.•Sertraline might aggravate the excitotoxicity if extracellular glutamate is high.
Mitochondrial damage and declines in ATP levels have been recently attributed to sertraline. The effects of sertraline on different parameters were investigated in washed platelets from 18 healthy male volunteers, after 24h of drug exposure. Sertraline toxicity was observed only at the highest concentrations, 30 and 100μM, which significantly reduced platelet viability to 76±3% and 20±2%, respectively. The same concentrations significantly decreased total ATP to 73±3% and 13±2%, respectively. Basal values of glycogen were not significantly affected by sertraline treatment. Glutamate uptake was significantly reduced after treatment with 3, 30 and 100μM, by 28±6%, 32±5% and 54±4%, respectively. Our data showed that sertraline at therapeutic concentrations does not compromise platelet viability and ATP levels, but they suggest that in a situation where extracellular glutamate levels are potentially increased, sertraline might aggravate an excitotoxic condition.