Norbert Dr. Dipl.-Chem. Hauel

288 EFFECT OF THE B1 ANTAGONIST BI 41488 IN DIFFERENT ANIMAL MODELS OF INFLAMMATORY PAIN

Background and Aims: The bradykinin 1 receptor is involved in both the initiation and progression of inflammatory response and pain (Marceau and Regoli, Nature Reviews Drug Discovery, 3, 845, 2004). The aim of this study was to test the B1 antagonist BI 41488 in two animal models of inflammatory pain. Material and methods: Binding affinity studies were performed using CHO cells expressing rat B1 receptors and H-kallidin as radioligand for the rat B1 receptors. Formalin paw test: The total number of flinches was evaluated after injection of formalin (50mL, 2%) into the plantar surface of the hind paw. Carrageenan paw test: Compound was administered 1 hour before carrageenan (50mL, 2%) into the plantar surface of the hindpaw. Mechanical and thermal hyperalgesia were tested 4 hours after carrageenan injection. Results: The affinity of BI 41488 for rat B1 receptors is 19nM. BI 41488, 30mg/kg p.o., 2 hours pre-treatment, significantly reduced the total number of flinches in the formalin paw test (50% effect). In the carraggeenan model, at 30mg/kg p.o., BI 41488 and indomethacin fully reversed mechanical and thermal hyperalgesia. Discussion: BI 41488 displayed a high potency for the rat B1 receptor and is orally active in different animal models of inflammatory pain. These results suggest the therapeutic utility of bradykinin B1 antagonists for the treatment of nociceptive pain.