title: Icatibant , the bradykinin B2 receptor antagonist with target to the interconnected kinin systems.
abstract: BACKGROUND
  HOE-140/ Icatibant is a selective, competitive antagonist to bradykinin (BK) against its binding to the kinin B2 receptor. Substitution of five non-proteogeneic amino acid analogues makes icatibant resistant to degradation by metalloproteases of kinin catabolism. Icatibant has clinical applications in inflammatory and vascular leakage conditions caused by an acute (non-controlled) production of kinins and their accumulation at the endothelium B2 receptor. The clinical manifestation of vascular leakage, called angioedema (AE), is characterized by edematous attacks of subcutaneous and submucosal tissues, which can cause painful intestinal consequences, and life-threatening complications if affecting the larynx. Icatibant is registered for the treatment of acute attacks of the hereditary BK-mediated AE, i.e., AE due to C1 inhibitor deficiency.
  
  
  METHODS
  This review discusses emerging knowledge on the kinin system: kinin pharmacological properties, biochemical characteristics of the contact phase and kinin catabolism proteases. It underlines the responsibility of the kinins in AE initiation and the potency of icatibant to inhibit AE formation by kinin-receptor interactions.
  
  
  CONCLUSIONS
  Icatibant antagonist properties protect BK-mediated AE patients against severe attacks, and could be developed for use in inflammatory conditions. More studies are required to confirm whether or not prolonged and frequent applications of icatibant could result in the impairment of the cardioprotective effect of BK.
authors.affiliation: Université Joseph Fourier Grenoble 1, GREPI/AGIM CNRS-UJF FRE 3405 and Centre de Référence des Angioedèmes CREAK, CHU Grenoble POBox 217, F-38043 Grenoble, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Charignon
authors.forename: Peter
authors.initials: P
authors.lastname: Späth
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Christian
authors.initials: C
authors.lastname: Drouet
mesh_terms: D000799:Angioedema / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D006801:Humans; D007705:Kinins / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065094:Bradykinin B2 Receptor Antagonists; D007705:Kinins; C065679:icatibant; D001920:Bradykinin