Grapiprant

Grapiprant (CJ-023423) is an orally active selective EP4 receptor antagonist. It exerts significant inhibitory effects on paw edema, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats.

Compared with other human prostaglandin receptor subtypes, grapiprant shows high selectivity for the human EP4 receptor. It also inhibits the PGE2-induced increase of intracellular cAMP in human and rat EP4 receptor-expressing cells, with pA2 values of 8.3 nM and 8.2 nM respectively.

In vivo, oral administration of grapiprant markedly alleviates thermal hyperalgesia induced by intraplantar PGE2 injection (ED50 = 12.8 mg/kg). It is also effective in acute and chronic inflammatory pain models.

In the carrageenan model, grapiprant significantly reduces mechanical hyperalgesia. Furthermore, it effectively reverses chronic inflammatory pain responses triggered by complete Freund’s adjuvant and produces anti-hyperalgesia effects in animal models of inflammatory pain.

Grapiprant is approved and widely used for the management of pain associated with osteoarthritis in dogs. It is a non-cyclooxygenase inhibiting nonsteroidal anti-inflammatory drug (NSAID).