Open AccessGrapiprant: an EP 4 prostaglandin receptor antagonist and novel therapy for pain and inflammation
Author(s) -
Kirkby Shaw Kristin,
RauschDerra Lesley C.,
Rhodes Linda
Publication year - 2016
Publication title -
veterinary medicine and science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.485
H-Index - 11
ISSN - 2053-1095
DOI - 10.1002/vms3.13
Subject(s) - inflammation , receptor , prostanoid , prostaglandin , homeostasis , prostaglandin e , medicine , pharmacology , prostaglandin e2 receptor , prostaglandin e2 , receptor antagonist , chemistry , immunology , endocrinology , antagonist , agonist
Abstract There are five active prostanoid metabolites of arachidonic acid ( AA ) that have widespread and varied physiologic functions throughout the body, including regulation of gastrointestinal mucosal blood flow, renal haemodynamics and primary haemostasis. Each prostanoid has at least one distinct receptor that mediates its action. Prostaglandin E 2 ( PGE 2 ) is a prostanoid that serves important homeostatic functions, yet is also responsible for regulating pain and inflammation. PGE 2 binds to four receptors, of which one, the EP 4 receptor, is primarily responsible for the pain and inflammation associated with osteoarthritis ( OA ). The deleterious and pathologic actions of PGE 2 are inhibited in varying degrees by steroids, aspirin and cyclo‐oxygenase inhibiting NSAID s; however, administration of these drugs causes decreased production of PGE 2 , thereby decreasing or eliminating the homeostatic functions of the molecule. By inhibiting just the EP 4 receptor, the homeostatic function of PGE 2 is better maintained. This manuscript will introduce a new class of pharmaceuticals known as the piprant class. Piprants are prostaglandin receptor antagonists ( PRA ). This article will include basic physiology of AA, prostanoids and piprants, will review available evidence for the relevance of EP 4 PRA s in rodent models of pain and inflammation, and will reference available data for an EP 4 PRA in dogs and cats. Piprants are currently in development for veterinary patients and the purpose of this manuscript is to introduce veterinarians to the class of drugs, with emphasis on an EP 4 PRA and its potential role in the control of pain and inflammation associated with OA in dogs and cats.