Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR

Diener, Hans‐Christoph; Abdullatif, Alkhedr; Busse, O.; Hacke, Werner; Zingmark, Per-Henrik; Jonsson, Niclas; Basun, Hans

doi:10.1007/s004150200065

Cited by 33 publications

(14 citation statements)

References 10 publications

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“…520, 521 The NMDA antagonist AR-R15896AR was tested in a clinical trial, but side effects, including psychiatric disturbances, meant that the agent could not be tolerated by the patient. 522 A preliminary study of the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist ZK 200775 showed that the medication led to declines in consciousness and possible neurological worsening. Studies of the glycine antagonist gavestinel found that the medication was relatively safe, but the likelihood of favorable outcomes was not improved.…”

Section: Neuroprotective Agentsmentioning

confidence: 99%

Guidelines for the Early Management of Adults With Ischemic Stroke

Adams

Zoppo²,

Alberts

et al. 2007

Stroke

2,123

483

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Purpose-Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods-Members of the panel were appointed

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Section: Neuroprotective Agentsmentioning

confidence: 99%

Guidelines for the Early Management of Adults With Ischemic Stroke

Adams

Zoppo²,

Alberts

et al. 2007

Stroke

2,123

483

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“…This receptor is known to have dual effects; it promotes neuronal death or survival in primary neuronal cultures in vitro and in the rat brain in vivo, depending on the level of receptor activity [69]. This may explain why in some clinical trials using a low-affinity blocker of the NMDA ion channel, mortality in patients with acute ischemic stroke was not reduced [70]. …”

Section: Perspective Therapiesmentioning

confidence: 99%

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

et al. 2016

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Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.

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“…738 Several N-methyl-d-aspartate antagonists have been tested in clinical trials, with largely negative results and increased rates of serious adverse events. [739][740][741][742][743][744][745][746][747][748][749][750][751][752] A 2003 systematic review of the excitatory amino acid modulator trials found no rates of improvements in either death or favorable outcomes with treatment. 753 Lubeluzole, which is thought to downregulate the glutamate-activated nitric oxide synthase pathway, was tested in several clinical trials, including one that evaluated the combination of the medication and intravenous rtPA.…”

Section: Pharmacological Agentsmentioning

confidence: 99%

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

Jauch¹,

Saver²,

Adams³

et al. 2013

Stroke

5,372

1,801

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Background and Purpose-The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates. Methods-Members of the writing committee were appointed by the American Stroke Association Stroke Council's Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council's Level of Evidence grading algorithm. Results-The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. Guidelines for the Early Management of PatientsThis statement was approved by the American Heart Association Science Advisory and Coordinating Committee on December 12, 2012. A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By Topic" link or the "By Publication Date" link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.The Executive Summary is available as an online-only Data Supplement with this article at http://stroke.ahajournals.org/lookup/suppl/ doi:10.1161/STR.0b013e318284056a/-/DC1.The American Heart Association requests that this document be cited as follows: Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan PW Jr, Qureshi AI, Rosenfield K, Scott PA, Summers DR, Wang DZ, Wintermark M, Yonas H; on behalf of the American Heart Association Stroke Council, Council on Cardio...

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Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR

Cited by 33 publications

References 10 publications

Guidelines for the Early Management of Adults With Ischemic Stroke

Guidelines for the Early Management of Adults With Ischemic Stroke

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

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