CJ-023,423 (Grapiprant) a potential novel active compound with antihyperalgetic properties for veterinary patients

Abstract

Companion animals are now living longer and so are more commonly manifesting age- and pain-related disease. Nonsteroidal antiinflammatory drugs are the most used drug in osteoarthritis and inflammatory pain of various aetiologies. Despite their safety profiles have been amended from the COX-non selective to the COX-2 selective inhibitor class, some adverse effects are still of concern especially in long term treatments. One prostaglandin (PG) downstream from the cyclooxygenase enzyme, PGE2, has been recognized as a pivotal mediator of pain and inflammation. The actions of PGE2 are produced by its interaction with four G-protein coupled receptors (EP1, EP2, EP3 and EP4). The EP4 receptor mediates PGE2-elicited sensitization of sensory neurons and studies have demonstrated that EP4 is a major receptor in mediating pain associated with both rheumatoid and osteoarthritis and in inflammation. CJ-023,423 (grapiprant) is a competitive antagonist of human and rat prostanoid EP4 receptors, under development for the control of pain and inflammation associated with osteoarthritisfor use in humans and dogs. A recent study has shown the good safety profile of this active ingredient in dogs. Despite this molecule is still far to be marketed because it pharmacokinetic/pharmacodynamics profile is need to be fully elucidated yet, it might be an interesting active ingredient for the veterinary medicine.