Memantine, an uncompetitive low affinity NMDA open-channel antagonist improves clinical rating scores in a multiple infarct embolic stroke model in rabbits

Brain Research
Paul A Lapchak

Abstract

The blockade of NMDA receptors has been pursued as a strategy to reduce the consequences of acute ischemic stroke (AIS) and NMDA receptors remain a valid therapeutic target to treat AIS. Because the pharmacological and toxicity profile of memantine in Alzheimer's disease patients appears to be good, we determined whether memantine would be effective at improving behavioral performance following embolic strokes in rabbits. For these studies, we used a rabbit multiple infarct ischemia model with a well-defined behavioral endpoint. In this study, memantine dissolved in PBS was given intravenously either as a bolus injection (over 1 min) or infused over 60 min. The P(50) of the control groups measured 24 h after embolization were 1.12 +/- 0.18 mg and 1.08 +/- 0.23 mg for the bolus injected and infused groups, respectively. Bolus injections of memantine at 1 mg/kg and 10 mg/kg were not effective at altering the P(50) value and memantine at a dose of 25 mg/kg was lethal. However, slowly infused memantine (25 mg/kg) significantly increased the P(50) value to 2.31 +/- 0.48 mg and 3.13 +/- 1.13 mg when given 5 and 60 min following embolization, respectively. Memantine administered 180 min following embolization also increased the P(50) ...Continue Reading

Associated Clinical Trials

May 22, 2014·Jennifer Majersik

References

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Jun 16, 2004·Alzheimer Disease and Associated Disorders·Marcel G RikkertFrans Verhey

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Citations

Oct 24, 2009·Clinical Interventions in Aging·Stuart J Thomas, George T Grossberg
Sep 19, 2007·Expert Opinion on Emerging Drugs·Paul A Lapchak, Dalia M Araujo
Nov 20, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Melissa TrotmanRobert Fern
Aug 11, 2012·Stroke; a Journal of Cerebral Circulation·Axel MontagneDenis Vivien
Jun 19, 2014·Stroke; a Journal of Cerebral Circulation·Héctor E López-ValdésKevin C Brennan
Aug 2, 2018·Reviews in the Neurosciences·Seyed Mohammad Seyedsaadat, David F Kallmes
Sep 29, 2020·Neural Regeneration Research·Hilda MartInez-CoriaHéctor E López-Valdés
Aug 10, 2019·Neural Regeneration Research·Paul A LapchakAli Khoynezhad
Jul 20, 2021·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Nahid Beladi MoghadamMohammad Sistanizad

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