Document Detail


Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size.
MedLine Citation:
PMID:  15321733     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prior work has demonstrated that melanin-concentrating hormone-1 (MCH-1) receptor antagonism decreases food intake and body weight in obese rodents. The purpose of this study was to determine if the MCH-1 receptor antagonist-mediated hypophagia was due a decrease in meal size, meal frequency, or both. We performed a meal pattern analysis in free-feeding hyperphagic diet-induced obese (DIO) rats treated with 1, 3 or 10 mg/kg p.o. of the MCH-1 receptor antagonist T-226296 (a (-)enantiomer of N-[6-(dimethylamino)-methyl]-5,6,7,8-tetrahydro-2-naphthalenyl]-4'-fluoro[1,1'-biphenyl]-4 carboxamide). Food intake was continuously monitored for 24 h using a BioDAQ food intake monitoring system. A total of 10 mg/kg T-226296 significantly decreased body weight and 24-h food intake, and had no effect on locomotor activity. The decrease in food intake was due to a reduction in meal size, not meal frequency. We conclude that MCH-1 receptor antagonism with T-226296 decreases food intake in DIO rats by selectively reducing meal size, and that the reduced food intake is not due to a generalized behavioral malaise.
Authors:
Timothy J Kowalski; Constance Farley; Mary E Cohen-Williams; Geoffrey Varty; Brian D Spar
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  497     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-23     Completed Date:  2005-08-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  41-7     Citation Subset:  IM    
Affiliation:
Cardiovascular/Metabolic Disease, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. timothy.kowalski@spcorp.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Biphenyl Compounds / administration & dosage,  chemistry,  pharmacology
Body Weight / drug effects
Dose-Response Relationship, Drug
Eating / drug effects*
Feeding Behavior / drug effects*
Male
Motor Activity / drug effects
Naphthalenes / administration & dosage,  chemistry,  pharmacology
Obesity / drug therapy
Rats
Rats, Sprague-Dawley
Receptors, Pituitary Hormone / antagonists & inhibitors*
Stereoisomerism
Time Factors
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Naphthalenes; 0/Receptors, Pituitary Hormone; 0/T-226296; 0/melanin-concentrating hormone receptor

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