Clazosentan

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Clazosentan
Clazosentan.svg
Clinical data
Trade names Pivlaz
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
  • 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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C25H23N9O6S
Molar mass 577.58 g·mol−1
3D model (JSmol)
  • 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=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.

Contents

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]

Related Research Articles

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A cerebral arteriovenous malformation is an abnormal connection between the arteries and veins in the brain—specifically, an arteriovenous malformation in the cerebrum.

<span class="mw-page-title-main">Intracranial aneurysm</span> Cerebrovascular disorder

An intracranial aneurysm, also known as a cerebral aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery or vein causes a localized dilation or ballooning of the blood vessel.

<span class="mw-page-title-main">Aneurysm</span> Bulge in the wall of a blood vessel

An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus for clot formation (thrombosis) and embolization. As an aneurysm increases in size, the risk of rupture, which leads to uncontrolled bleeding, increases. Although they may occur in any blood vessel, particularly lethal examples include aneurysms of the circle of Willis in the brain, aortic aneurysms affecting the thoracic aorta, and abdominal aortic aneurysms. Aneurysms can arise in the heart itself following a heart attack, including both ventricular and atrial septal aneurysms. There are congenital atrial septal aneurysms, a rare heart defect.

<span class="mw-page-title-main">Interventional radiology</span> Medical subspecialty

Interventional radiology (IR) is a medical specialty that performs various minimally-invasive procedures using medical imaging guidance, such as x-ray fluoroscopy, computed tomography, magnetic resonance imaging, or ultrasound. IR performs both diagnostic and therapeutic procedures through very small incisions or body orifices. Diagnostic IR procedures are those intended to help make a diagnosis or guide further medical treatment, and include image-guided biopsy of a tumor or injection of an imaging contrast agent into a hollow structure, such as a blood vessel or a duct. By contrast, therapeutic IR procedures provide direct treatment—they include catheter-based medicine delivery, medical device placement, and angioplasty of narrowed structures.

<span class="mw-page-title-main">Subarachnoid hemorrhage</span> Bleeding into the subarachnoid space

Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, weakness, numbness, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.

<span class="mw-page-title-main">Intracranial hemorrhage</span> Hemorrhage, or bleeding, within the skull

Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds, subarachnoid bleeds, epidural bleeds, and subdural bleeds.

<span class="mw-page-title-main">Cerebral angiography</span> Angiography that produces images of blood vessels in and around the brain

Cerebral angiography is a form of angiography which provides images of blood vessels in and around the brain, thereby allowing detection of abnormalities such as arteriovenous malformations and aneurysms. It was pioneered in 1927 by the Portuguese neurologist Egas Moniz at the University of Lisbon, who also helped develop thorotrast for use in the procedure.

<span class="mw-page-title-main">Nimodipine</span> Antihypertensive drug of the calcium channel blocker class

Nimodipine, sold under the brand name Nimotop among others, is calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage. It was originally developed within the calcium channel blocker class as it was used for the treatment of high blood pressure, but is not used for this indication.

Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.

The International Subarachnoid Aneurysm Trial (ISAT) was a large multicentre, prospective randomised clinical medical trial, comparing the safety and efficacy of endovascular coil treatment and surgical clipping for the treatment of brain aneurysms. The study began in 1994. The first results were published in The Lancet in 2002, and the 10 year data were published again in The Lancet in early September 2005. 2,143 study participants were mostly drawn from U.K. hospitals with the rest drawn from North American and European hospitals.

<span class="mw-page-title-main">Endothelin</span>

Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases.

<span class="mw-page-title-main">Intracerebral hemorrhage</span> Type of intracranial bleeding that occurs within the brain tissue itself

Intracerebral hemorrhage (ICH), also known as hemorrhagic stroke, is a sudden bleeding into the tissues of the brain, into its ventricles, or into both. An ICH is a type of bleeding within the skull and one kind of stroke. Symptoms can vary dramatically depending on the severity, acuity, and location (anatomically) but can include headache, one-sided weakness, numbness, tingling, or paralysis, speech problems, vision or hearing problems, memory loss, attention problems, coordination problems, balance problems, dizziness or lightheadedness or vertigo, nausea/vomiting, seizures, decreased level of consciousness or total loss of consciousness, neck stiffness, and fever.

<span class="mw-page-title-main">Ticagrelor</span> Coronary medication

Ticagrelor, sold under the brand name Brilinta among others, is a medication used for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. It acts as a platelet aggregation inhibitor by antagonising the P2Y12 receptor. The drug is produced by AstraZeneca.

Joshua B. Bederson is an American neurosurgeon, Leonard I. Malis, MD/Corinne and Joseph Graber Professor of Neurosurgery, and System Chair of Neurosurgery at the Mount Sinai Health System in New York City. He is a Fellow of the American College of Surgeons, and an attending neurosurgeon at The Mount Sinai Hospital.

<span class="mw-page-title-main">Endovascular coiling</span>

Endovascular coiling is an endovascular treatment for intracranial aneurysms and bleeding throughout the body. The procedure reduces blood circulation to the aneurysm through the use of microsurgical detachable platinum wires, with the clinician inserting one or more into the aneurysm until it is determined that blood flow is no longer occurring within the space. It is one of two main treatments for cerebral aneurysms, the other being surgical clipping. Clipping is an alternative to stenting for bleeding.

Interventional neuroradiology (INR) also known as neurointerventional surgery (NIS), endovascular therapy (EVT), endovascular neurosurgery, and interventional neurology is a medical subspecialty of neurosurgery, neuroradiology, intervention radiology and neurology specializing in minimally invasive image-based technologies and procedures used in diagnosis and treatment of diseases of the head, neck, and spine.

Cerebral vasospasm is the prolonged, intense vasoconstriction of the larger conducting arteries in the subarachnoid space which is initially surrounded by a clot.

Acoustocerebrography (ACG) is a medical test used to diagnose changes and problems in the brain and the central nervous system. It allows for the noninvasive examination of the brain's cellular and molecular structure. It can also be applied as a means to diagnose and monitor intracranial pressure, for example as incorporated into continuous brain monitoring devices. ACG uses molecular acoustics, in audible and ultrasound frequency ranges, to monitor changes. It may use microphones, accelerometers, and multifrequency ultrasonic transducers. It does not use any radiation and is completely free of any side effects. ACG also facilitates blood flow analysis as well as the detection of obstructions in cerebral blood flow (from cerebral embolism) or bleeding (from cerebral hemorrhage).

Alexander Coon is an American neurosurgeon who is the Director of Endovascular and Cerebrovascular Neurosurgery at the Carondelet Neurological Institute of St. Joseph's and St. Mary's Hospitals in Tucson, Arizona. He was previously the Director of Endovascular Neurosurgery at the Johns Hopkins Hospital and an assistant professor of neurosurgery, Neurology, and Radiology at the Johns Hopkins Hospital. He is known for his work in cerebrovascular and endovascular neurosurgery and his research in neuroendovascular devices and clinical outcomes in the treatment of cerebral aneurysms, subarachnoid hemorrhage, and AVMs.

Stephan A. Mayer is an American neurologist and critical care physician who currently serves as Director of Neurocritical Care and Emergency Neurology Services for the Westchester Medical Center Health System. Mayer is most noted for his research in subarachnoid and intracerebral hemorrhage, acute ischemic stroke, cardiac arrest, coma, status epilepticus, brain multimodality monitoring, therapeutic temperature modulation, and outcomes after severe brain injury. He has gained media attention for popularizing the concept that physicians have historically underestimated the brain’s resilience and capacity for recovery. He has authored over 400 original research publications, 200 chapters and review articles, and 370 abstracts.

References

  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.