Bradykinin is a nonapeptide hormone which can increase vessel permeability, dilate blood vessels and cause smooth muscle cells to contract. Icatibant is a long acting and potent peptide antagonist of bradykinin receptor B2 with IC50 value of 1.07nM and Ki value of 0.798nM, respectively, for receptor binding studies in guinea-pig ileum preparations[1][2]. Icatibant antagonized bradykinin-induced EDRF release and increase in cytosolic free calcium with IC50 value of 10nM and 1nM, respectively, in cultured bovine endothelial cells, and totally suppressed the bradykinin-induced PGI2 release from cultured endothelial cells of bovine aorta at concentration of 100nM[1]. Also Icatibant competitively inhibited the hydrolysis of L-Ala-p-nitroanilide by recombinant aminopeptidase N with Ki value of 9.1 μM. It potentiated angiotensin III and Lys-des-Arg9-bradykinin in the rabbit aorta at concentration of 10–30 μM[3]. Icatibant is usually used to treat for angioedema[4][5].
Icatibant acetate/艾替班特乙酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
B2tg mice (endothelium-specific overexpression of B2 receptors)
Intravenous or intraperitoneal injection
2 or 20 nmol
Single dose, 2 hours prior
To investigate the effect of icatibant on bradykinin-induced dermal extravasation. Results showed that icatibant almost completely inhibited bradykinin-induced extravasation.
Br J Pharmacol. 2018 May;175(10):1607-1620
Sprague-Dawley rats
Unilateral ureteral obstruction (UUO) model
Subcutaneous injection
200 μg subcutaneous injection, twice daily
Twice daily for 14 days
B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney.
Acta Pharmacol Sin. 2020 Dec;41(12):1597-1608
Mice
Db/db mice (type 2 diabetes model)
Subcutaneous injection
0.4 mg/kg/day
Once daily for 14 days
To investigate the effect of icatibant on the improvement of cardiac and renal function by Ang-(1–7) in db/db mice. Results showed that icatibant blocked the beneficial effects of Ang-(1–7) on cardiac vascular density and inflammatory cell infiltration.
Br J Pharmacol. 2015 Sep;172(18):4443-4453
Male Swiss mice
Cisplatin-induced peripheral neuropathy model
Intraperitoneal injection
100 nmol/kg
Single administration
To evaluate the therapeutic effect of Icatibant on cisplatin-induced mechanical allodynia, results showed that Icatibant significantly reduced mechanical allodynia from 0.5 to 2 hours after administration
Pharmaceutics. 2023 Mar 6;15(3):852
Male C57BL/6 mice
Anastrozole-induced pain model
Intraperitoneal injection
100 nmol/kg
Single administration
Icatibant reduced the mechanical allodynia and muscle strength loss induced by anastrozole.
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