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Two novel, putative mechanisms of action for citalopram-induced platelet inhibition.

Roweth, Harvey G, Cook, Aaron A, Moroi, Masaaki, Bonna, Arkadiusz M, Jung, Stephanie M, Bergmeier, Wolfgang, Sage, Stewart O and Jarvis, Gavin E. (2018) Two novel, putative mechanisms of action for citalopram-induced platelet inhibition. Scientific reports, 8 (1). p. 16677. ISSN 2045-2322

Item Type: Article


Citalopram, a selective serotonin reuptake inhibitor (SSRI), inhibits platelet function in vitro. We have previously shown that this action is independent of citalopram's ability to block serotonin uptake by the serotonin transporter and must therefore be mediated via distinct pharmacological mechanisms. We now report evidence for two novel and putative mechanisms of citalopram-induced platelet inhibition. Firstly, in platelets, citalopram blocked U46619-induced Rap1 activation and subsequent platelet aggregation, but failed to inhibit U46619-induced increases in cytosolic Ca. Similarly, in neutrophils, citalopram inhibited Rap1 activation and downstream functions but failed to block PAF-induced Ca mobilisation. In a cell-free system, citalopram also reduced CalDAG-GEFI-mediated nucleotide exchange on Rap1B. Secondly, the binding of anti-GPVI antibodies to resting platelets was inhibited by citalopram. Furthermore, citalopram-induced inhibition of GPVI-mediated platelet aggregation was instantaneous, reversible and displayed competitive characteristics, suggesting that these effects were not caused by a reduction in GPVI surface expression, but by simple competitive binding. In conclusion, we propose two novel, putative and distinct inhibitory mechanisms of action for citalopram: (1) inhibition of CalDAG-GEFI/Rap1 signalling, and (2) competitive antagonism of GPVI in platelets. These findings may aid in the development of novel inhibitors of CalDAG-GEFI/Rap1-dependent nucleotide exchange and novel GPVI antagonists.

Roweth (2018) Two novel, putative mechanisms of action for citalopram-induced platelet inhibition, SciRep.pdf - Published Version
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Depositing User: Gavin Jarvis


Item ID: 14419
Identification Number:
ISSN: 2045-2322
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ORCID for Gavin E. Jarvis: ORCID iD

Catalogue record

Date Deposited: 25 Jan 2022 12:46
Last Modified: 25 Jan 2022 12:46


Author: Gavin E. Jarvis ORCID iD
Author: Harvey G Roweth
Author: Aaron A Cook
Author: Masaaki Moroi
Author: Arkadiusz M Bonna
Author: Stephanie M Jung
Author: Wolfgang Bergmeier
Author: Stewart O Sage
Author: Gavin E. Jarvis

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences
Sciences > Pharmacy and Pharmacology

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