Inhibitory mechanisms of gabapentin, an antiseizure drug, on platelet aggregation

Abstract

Abstract Gabapentin (Neurontin) is an analogue of gamma-aminobutyric acid (GABA) that is effective against partial seizures. Gabapentin has been reported to modulate serotonin release from platelets, but the effects of gabapentin on platelet activation have not been explored. In this study, gabapentin concentration-dependently (60–240 μm) inhibited platelet aggregation in washed platelets stimulated by collagen (1 μg mL−1), ADP (20 μm) and arachidonic acid (60 μm). Gabapentin (120 and 240 μm) also concentration-dependently inhibited collagen (1 μg mL−1)-induced phospho-inositide breakdown, intracellular Ca2+ mobilization, thromboxane A2 formation, and p38 MAPK phosphorylation in human platelets. In conclusion, the most important findings of this study suggest that gabapentin inhibits platelet aggregation, at least in part, through the phospholipase C-inositol 1,4,5-trisphosphate-thromboxane A2-Ca2+ pathway. Thus, it is possible that gabapentin treatment, alone or in combination with other antiplatelet drugs, may induce or potentiate inhibition of platelet aggregation, which may affect haemostasis in-vivo.