Clazosentan (Ro 61-1790) is a selective endothelin A (ETA) receptor antagonist. Clazosentan inhibits ET-1-mediated vasoconstriction. Clazosentan prevents cerebral vasospasm, vasospasm-related cerebral infarction[1][5].
Clazosentan (0.1 μM) inhibits the ETA receptor in cerebral arteries[3].
Clazosentan is a substrate of the organic anion-transporting polypeptide (OATP) 1B1/1B3[5].
Clazosentan (10 μM, 0.05 mL/kg, intracisternal injection) inhibits the contractile responses to ET-1 in rats[2].
Clazosentan (10 mg/kg, s.c.) inhibits IL-33-induced hypernociception in mice[4].
| Animal Model: | Rats[2] |
| Dosage: | 10 μM, 0.05 mL/kg |
| Administration: | Intracisternal injection |
| Result: | Inhibited the contractile responses to ET-1, without preventing SAH-induced upregulation of ET receptors in cerebral arteries. |
[1]. Juif PE, et al. Clinical Pharmacology of Clazosentan, a Selective Endothelin A Receptor Antagonist for the Prevention and Treatment of aSAH-Related Cerebral Vasospasm. Front Pharmacol. 2021 Feb 4;11:628956.
[2]. Povlsen GK, et al. MEK1/2 inhibitor U0126 but not endothelin receptor antagonist clazosentan reduces upregulation of cerebrovascular contractile receptors and delayed cerebral ischemia, and improves outcome after subarachnoid hemorrhage in rats. J Cereb Blood Flow Metab. 2015 Feb;35(2):329-37.
[3]. Vatter H, et al. Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: inhibitory effect on endothelin(A) receptor-mediated contraction. J Neurosurg. 2005 Jun;102(6):1101-7.
[4]. Verri WA Jr, Guerrero AT, Fukada SY, Valerio DA, Cunha TM, Xu D, Ferreira SH, Liew FY, Cunha FQ. IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2723-8.
[5]. Juif PE, et al. Influence of Rifampin-Mediated Organic Anion-Transporting Polypeptide 1B1/1B3 Inhibition on the Pharmacokinetics of Clazosentan. Clin Transl Sci. 2019 Sep;12(5):440-444.