Grapiprant: Uses, Side effects and Mechanism of action

What is Grapiprant ?

Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. It has been shown to have anti-inflammatory effects in rat models of acute and chronic inflammation and clinical studies in people with osteoarthritis. The current state of knowledge suggests the possibility of using it in oncological therapy.

Mechanism of action

PGE2 is a key mediator of pain and inflammation and has its effect through binding to the EP4 receptor. Grapiprant directly and specifically blocks the EP4 receptor, and therefore blocks PGE2‐elicited pain and inflammation. An EP4 PRA, such as grapiprant, which has been demonstrated to provide relief from arthritic pain in canine clinical patients, acts without affecting the synthesis and widespread activity of PGE2 and other prostanoids.

Side effects of Grapiprant

Grapiprant side effects include vomiting, diarrhoea, loss of appetite, blood or mucus in the stool and a drop in blood protein levels. This medium-acting drug should stop working within a few days, although the effects may be longer in pets with liver or kidney disease.

The relative lack of toxic effects with grapiprant compared to those that have been reported in dogs treated with COX‐inhibiting NSAIDs is not surprising. Grapiprant is a targeted approach to pain management – it selectively blocks the EP4 receptor, does not interfere with the production of prostanoids, and therefore does not affect the other PG receptor pathways that are affected in animals treated with COX inhibitor NSAIDs.

References

[1] PAWEŁ GUMUŁKA. Quantification of Grapiprant and Its Stability Testing under Changing Environmental Conditions.[J]. Biomedicines, 2022. DOI:10.3390/biomedicines10112821.

[2] IRENE SARTINI; Mario G. Grapiprant: A snapshot of the current knowledge[J]. Journal of veterinary pharmacology and therapeutics, 2021. DOI:10.1111/jvp.12983.