New mechanisms of action for platelet inhibition identified

Study by Gavin Jarvis on citalopram-induced platelet inhibition reports evidence for two novel and putative mechanisms of inhibition

Abstract: We report that citalopram, a selective serotonin reuptake inhibitor, inhibits platelet function via two novel and putative mechanisms. Firstly, in both platelets and neutrophils, citalopram blocks Ca²⁺-mediated Rap1 activation and downstream function. In a cell-free system, citalopram reduced CalDAG-GEFI-mediated nucleotide exchange on Rap1B suggesting that Rap1B/CalDAG may be the primary target for citalopram. Secondly, citalopram inhibited the binding of anti-GPVI antibodies and inhibited GPVI-mediated platelet aggregation instantaneously and reversibly, suggesting a simple competitive mechanism of action. These findings may aid in the development of novel inhibitors of CalDAG-GEFI/Rap1-dependent nucleotide exchange and novel GPVI antagonists.

Reference: Harvey G. Roweth, Aaron A. Cook, Masaaki Moroi, Arkadiusz M. Bonna, Stephanie M. Jung, Wolfgang Bergmeier, Stewart O. Sage, Gavin E. Jarvis  (2018), Two novel, putative mechanisms of action for citalopram-induced platelet inhibition, Scientific Reports volume 8, Article number: 16677