Document Detail


Ondansetron and fluoxetine reduce sleep apnea in mice lacking monoamine oxidase A.
MedLine Citation:
PMID:  19615472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prospective clinical trials addressing the role of serotonin (5-HT) in sleep apnea have indicated that the 5-HT uptake inhibitor fluoxetine is beneficial to some patients with obstructive apnea, whereas the 5-HT(3) receptor antagonist ondansetron seems of little value despite its efficacy in rat and dog models of sleep apnea (central and obstructive). Here, we examined the effect of these drugs in transgenic mice lacking monoamine oxidase A (Tg8), which exhibit approximately 3-fold higher rates of central sleep apnea than their wild-type counterparts (C3H), linked to their enhanced 5-HT levels. Acute ondansetron (2 mg kg(-1), intraperitoneal), acute fluoxetine (16 mg kg(-1)) and 13-day chronic fluoxetine (1 or 16 mg kg(-1)) decreased by approximately 80% the total (spontaneous and post-sigh) apnea index in Tg8 mice during non-rapid eye movement sleep, with no statistically significant effect on apnea in C3H mice. Our study shows that both drugs reduce the frequency of apneic episodes attributable to increased monoamine levels in this model of MAOA deficiency, and suggests that both may be effective in some patients with central sleep apneas.
Authors:
C Real; I Seif; J Adrien; P Escourrou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-15
Journal Detail:
Title:  Respiratory physiology & neurobiology     Volume:  168     ISSN:  1878-1519     ISO Abbreviation:  Respir Physiol Neurobiol     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-02     Completed Date:  2009-11-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140022     Medline TA:  Respir Physiol Neurobiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  230-8     Citation Subset:  IM    
Affiliation:
Univ Paris-Sud, EA 3544, Sérotonine et Neuropharmacologie, Châtenay-Malabry cedex, France. caroline.prenat@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Fluoxetine / pharmacology*
Mice
Mice, Inbred C3H
Mice, Knockout
Monoamine Oxidase / deficiency*
Ondansetron / pharmacology*
Plethysmography, Whole Body / methods
Respiratory Mechanics / drug effects*
Serotonin Antagonists / pharmacology*
Serotonin Uptake Inhibitors / pharmacology*
Sleep Apnea Syndromes / drug therapy,  genetics*
Wakefulness / drug effects
Chemical
Reg. No./Substance:
0/Serotonin Antagonists; 0/Serotonin Uptake Inhibitors; 54910-89-3/Fluoxetine; 99614-02-5/Ondansetron; EC 1.4.3.4/Monoamine Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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