Function of icatibant in hereditary angioedema



Icatibant, sold under the trade name Firazyr, is a plasma kallikrein inhibitor and the bradykinin B2 receptor antagonist, consisting of ten amino acids. Bradykinin is a vasoactive peptide, which is usually in response to a trauma. Bradykinin, as an inflammatory mediator, can cause blood vessels to dilate, can increase vascular permeability and can lead smooth muscle cells to contract. In the situation of C1-inhibitor deficiency, icatibant is able to replace bradykinin from B2 receptors for the treatment of angioedema.

Pharmacologic action

As an antagonist of bradykinin, an active oligopeptide of the kinin group proteins, icatibant can interrupt the binding between vasoactive bradykinin and B2 receptors, which has an inhibitory effect on bradykinin physiological functions. Bradykinin physiological functions, including enlarging the blood vessels, increasing vascular permeability and contracting airway and guts, are all based on the binding to B2 receptors. The increased amounts of bradykinin in patients with hereditary angioedema (HAE) promotes swelling, which commonly affects the extremities, intestinal tract and airway. Under the circumstances of C1-inhibitor deficiency due to the genetic factors, plasma kallikrein can be easily activated, which induces the production of bradykinin. While the bradykinin can't be degraded, icatibant provides another treatment by interfering the binding between bradykinin and its receptors. Therefore, the action of icatibant inhibits swelling caused by HAE to some extent.


Unlike the other drugs for the treatment of HAE, aiming at inhibiting the activity of plasma kallikrein, icatibant replaces bradykinin from B2 receptors to stop the fluid leakage from blood vessels caused by an excess of bradykinin. In clinical applications, icatibant is mainly used in patients with inflammatory and vascular leakage conditions and is approved as a treatment for the acute attacks of the hereditary angioedema. Also, icatibant blocking aminopeptidase N is under study. The blockage may have the potential to affect the metabolism process of regulatory peptides. And it's also investigated for treatment in liver disease, burns and burn infections.

Pharmacokinetics and metabolism

As a competitive antagonist of bradykinin B2 receptors, its constitution of 5 non-proteogeneic amino acid analogues permits icatibant to resist the degradation by metalloproteases of kinin catabolism. Metabolism studies reveal that proteolytic enzymes are involved in icatibant metabolism process to degrade it into inactive metabolites. And there is no evidence for the implication of cytochrome P450. The value of its water solubility is 1 mg/mL in laboratory. Icatibant is excreted in the urine at a rate below 10% after a route of elimination, while its mean elimination half-life is 1.4±0.4 hours after subcutaneous administration.


1. Bawolak MT, Fortin JP, Vogel LK, Adam A, Marceau F: The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors. Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11.

2. Delphine Charignon, MSc, Peter Späth, PhD, Ludovic Martin, MD PhD & Christian Drouet, PhD. Icatibant, the bradykinin B2 receptor antagonist with target to the interconnected kinin systems. Expert Opinion on Pharmacotherapy. 2012, 13(15):2233-2247

3. Chen, X., Ji, Z. L., & Chen, Y. Z. (2002). TTD: therapeutic target database. Nucleic acids research, 30(1), 412-415.

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