Clazosentan

Clazosentan
Clinical data
Trade names	Pivlaz
ATC code	C04AX33 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name 5-methyl-pyridin-2-sulfonic acid{6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridin-4-yl]-pyrimidin-4-yl}amide;
CAS Number	180384-56-9;
PubChem CID	6433095;
DrugBank	DB06677;
ChemSpider	4938283;
UNII	3DRR0X4728;
KEGG	D11664;
ChEMBL	ChEMBL109648;
CompTox Dashboard (EPA)	DTXSID60170955 ;
Chemical and physical data
Formula	C25H23N9O6S
Molar mass	577.58 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CN=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=CC(=NC=C3)C4=NNN=N4)OCCO)OC5=CC=CC=C5OC;
	InChI InChI=1S/C25H23N9O6S/c1-15-7-8-20(27-14-15)41(36,37)32-24-21(40-19-6-4-3-5-18(19)38-2)25(39-12-11-35)29-22(28-24)16-9-10-26-17(13-16)23-30-33-34-31-23/h3-10,13-14,35H,11-12H2,1-2H3,(H,28,29,32)(H,30,31,33,34); Key:LFWCJABOXHSRGC-UHFFFAOYSA-N;

Clazosentan (INN, brand name Pivlaz^[1]) is a drug belonging to the class of endothelin receptor antagonists.

Mechanism

The endothelin 1 receptor is one of the strongest known vasoconstrictors. After subarachnoidal bleedings, irritation of the blood vessels can lead to a vasospasm and thus to an ischaemia, an insufficient blood supply to brain tissue. One possible effect of this is, in turn, an ischaemic stroke.

Trials

In a randomized trial with patients who had aneurysmal subarachnoid bleeding and were being treated with endovascular coiling, 15 mg/h clazosentan significantly reduced vasospasm-related morbidity and all-cause mortality. Clazosentan, however, did not improve the neurological outcome as measured by the extended Glascow Outcome Scale.^[2]

References

^ "Idorsia receives Japanese PMDA approval of Pivlaz" (Press release). Idorsia. 20 January 2022. Retrieved 22 January 2022 – via GlobalNewsWire.
^ Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. (June 2012). "Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling". Stroke. 43 (6): 1463–1469. doi:10.1161/STROKEAHA.111.648980. PMID 22403047. S2CID 3113695.

[1] "Idorsia receives Japanese PMDA approval of Pivlaz" (Press release). Idorsia. 20 January 2022. Retrieved 22 January 2022 – via GlobalNewsWire.

[2] Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. (June 2012). "Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling". Stroke. 43 (6): 1463–1469. doi:10.1161/STROKEAHA.111.648980. PMID 22403047. S2CID 3113695.

[1]

[2]