Document Detail

Antagonism of Substance P and Perception of Breathlessness in Patients with Chronic Obstructive Pulmonary Disease.
MedLine Citation:
PMID:  24582719     Owner:  NLM     Status:  Publisher    
The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of breathlessness by administering aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor signaling. Individual targeted resistive load breathing (RLB) was used to provoke breathlessness. In Study 1, sixteen patients (age, 70±6 years) with chronic obstructive pulmonary disease (COPD) reported similar ratings of breathlessness during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not with placebo, there were significant increases in blood levels of substance P (+54±39%) and beta-endorphin (+27±17%). A similar design was used in Study 2 except that naloxone (10mg) was administered intravenously prior to RLB to block any effect of endogenous opioids. Nine patients with COPD reported comparable breathlessness ratings during RLB between aprepitant and placebo. Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. With selective antagonism of NK-1 signaling, there was co-transmission of substance P and beta-endorphin neuropeptides.
Donald A Mahler; Alex H Gifford; Aamir Gilani; Laurie A Waterman; Jennifer Hilton; Andrew S Chang; Brian R Kupchak; William J Kraemer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-25
Journal Detail:
Title:  Respiratory physiology & neurobiology     Volume:  -     ISSN:  1878-1519     ISO Abbreviation:  Respir Physiol Neurobiol     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-3-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140022     Medline TA:  Respir Physiol Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
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