Psychotropic and neurodegenerative drugs modulate platelet activity via the PAF pathway.
Psychotropic and neurodegenerative drugs modulate platelet activity via the PAF pathway.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kavála, GR · Author affiliation
Hephaestus, Laboratory, School of Chemistry, Faculty of Sciences, Democritus University of Thrace, St Lukas, 65404, Kavala, Greece. Electronic address: sakosid@chem.duth.gr.Location evidence
Thessaloníki, GR · Author affiliation
Laboratory of Environmental Pollution Control, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24, Thessaloniki, Greece; Centre for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center, Thessaloniki, 10th km, Thessaloniki-Thermi Rd, GR 57001, Greece. Electronic address: dlambro@chem.auth.gr.Location evidence
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Original abstract
Mild psychiatric conditions such as anxiety and depression, as well as severe disorders like schizophrenia and neurodegenerative diseases, are increasingly recognized as systemic inflammatory conditions. Platelets possess both hemostatic and immunomodulatory roles in these situations, with sharing key molecular pathways with the central nervous system, offering thus a valuable peripheral model for evaluating psychotropic drug effects. Platelet-activating factor (PAF), a potent thrombo-inflammatory mediator, has emerged as a potential link between the two systems, yet its involvement in drug responses remains understudied. This study systematically investigates the effects of psychotropic drugs (i.e. antidepressants, antipsychotics and anxiolytics), and neuroprotective (anti-Alzheimer's/Anti-Parkinson's) drugs on platelet aggregation, focusing on PAF-pathway in comparison to a control platelet agonist, ADP. Using ex vivo light transmission aggregometry, we determined IC50 values for each drug and analyzed the impact of selected drug combinations, in which the NSAID diclofenac was also included. Results revealed that most of the compounds assessed inhibited more effectively the PAF-induced aggregation of platelets compared to their effect on the ADP-pathway, with perphenazine showing the greatest anti-PAF potency. Several drug combinations, notably those including alprazolam and diclofenac, demonstrated significant synergistic effects. These findings suggest that commonly prescribed psychotropic drugs and medications for neurodegenerative disorders can influence platelet activity, mostly through the PAF-pathway, and that their interactions with NSAIDs may amplify their efficacy. Nevertheless, some drugs and their combinations induced lysis of platelets at much higher concentrations than their IC50 values, which stems safety concerns for their use.