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Original Research |

Antitussive Effects of Memantine in Guinea PigsMemantine for Cough

Jaclyn A. Smith, PhD; Emma C. Y. Hilton, MBChB; Loren Saulsberry, BS; Brendan J. Canning, PhD
Author and Funding Information

From the Department of Medicine (Drs Smith and Canning and Ms Saulsberry), Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, and Respiratory Research Group (Drs Smith and Hilton), The University of Manchester, University Hospital of South Manchester, Manchester, England.

Correspondence to: Brendan J. Canning, PhD, Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Cir, Baltimore, MD 21224; e-mail: bjc@jhmi.edu


Funding/Support: This study was supported by a Medical Research Council Clinician Scientist Fellowship, a Medical Research Council Training Fellowship, and the National Institutes of Health [Grant HL083192].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(4):996-1002. doi:10.1378/chest.11-0554
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Background:  The treatment of cough is a significant clinical unmet need because there is little evidence that current therapies are effective. Based on evidence supporting a role for N-methyl d-aspartate receptors (NMDARs) in cough, we hypothesized that memantine, a low-affinity, uncompetitive NMDAR channel blocker in routine use for the treatment of Alzheimer disease, could be an effective, well-tolerated, antitussive therapy. The aim of this study was to establish preclinical evidence that memantine has antitussive effects.

Methods:  We studied the influence of memantine on experimentally induced coughing in response to citric acid and bradykinin inhalation in guinea pigs. We also compared the potency and efficacy of memantine as an antitussive to other NMDAR antagonists, dextromethorphan and ketamine, and to the γ-aminobutyric acid class B receptor agonist baclofen.

Results:  Compared with control subjects, 10 mg/kg memantine significantly reduced the cumulative number of coughs evoked by both citric acid (median, 24.0 [interquartile range (IQR), 13.0-25.5] vs 1.5 [IQR, 0.3-10.3] coughs; P = .012) and bradykinin aerosols (median, 16.0 [IQR, 9.5-18.5] vs 0.0 [IQR, 0-0.75] coughs; P = .002). Memantine 10 mg/kg produced a similar reduction in the cumulative number of coughs to baclofen 3 mg/kg and demonstrated comparatively greater cough suppression than 30 mg/kg dextromethorphan or 30 mg/kg ketamine. This dose of memantine produced no sedative or respiratory depressive effects.

Conclusions:  This study illustrates that memantine has marked antitussive effects in guinea pigs, most likely mediated through NMDAR channel blockade. Memantine, therefore, has the potential to be a safe, effective, and well-tolerated antitussive agent.

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