Grapiprant Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Prostaglandin E
2 (PGE
2) activates four E prostanoid (EP) receptors, EP
1-4. EP
4 is a G
s protein-coupled receptor that, by elevating the second messenger cAMP, plays important roles in bone formation and resorption, cancer, and atherosclerosis. CJ-023423 is a potent and selective antagonist of the EP
4 receptor (K
i = 13 and 20 nM for human and rat EP
4, respectively). It inhibits PGE
2-evoked elevation in intracellular cAMP in cells and,
in vivo, reduces thermal hyperalgesia induced by intraplantar injection of PGE
2. CJ-023423 reduces acute and chronic inflammatory pain in different mouse models.
Verwenden
CJ-023423 is a potent and selective antagonist of E prostanoid 4 (EP4) receptor.
Biologische Funktion
Grapiprant (CJ-023423) is an orally available, a potent and selective EP4 receptor antagonist that exhibits significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. Grapiprant is highly selective for the human EP4 receptor over other human prostanoid receptor subtypes. It also inhibits PGE2-evoked elevation in intracellular cAMP at the human and rat EP4 receptors with pA2 of 8.3 and 8.2 nM, respectively. In vivo, oral administration of grapiprant significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE2 (ED50 = 12.8 mg/kg). It is also effective in models of acute and chronic inflammatory pain. Grapiprant significantly reduces mechanical hyperalgesia in the carrageenan model. Furthermore, it significantly reverses complete Freund′s adjuvant-induced chronic inflammatory pain response. It produces antihyperalgesic effects in animal models of inflammatory pain. Grapiprant is approved and widely used for treatment of osteoarthritis related pain in dogs. Grapiprant is classify as a non-cyclooxygenase inhibiting non-steroidal anti-inflammatory drug (NSAID).
Nebenwirkungen
Possible side effects of Grapiprant include: vomiting, drowsiness, diarrhoea, loss of appetite, blood or mucus in the stool, and reduced blood protein levels. The degree of reaction can vary from mild to severe, but if your dog experiences a loss of appetite or abnormal faeces, you should contact your veterinarian promptly.
Grapiprant Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
