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Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models.
MedLine Citation:
PMID:  23267345     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH(1)). S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, its action on various models of obesity was studied. Acute intra-cerebroventricular (i.c.v.) administration of S38151 in wild-type rats counteracted the effect of the stable precursor of melanin-concentrating hormone (MCH), NEI-MCH, in a dose-dependent manner (from 0.5 to 50 nmol/kg). In genetically obese Zucker fa/fa rats, daily i.c.v. administration of S38151 induced dose-dependent (5, 10, and 20 nmol/kg) inhibition of food intake, water intake, and body weight gain, as well as increased motility (maximal effect observed at 20 nmol/kg). In Zucker fa/fa rats, intraperitoneal injection of S38151 (30 mg/kg) induced complete inhibition of food consumption within 1 h. Daily intraperitoneal injection of S38151 (10 and 30 mg/kg) into genetically obese ob/ob mice or diet-induced obese mice is able to limit body weight gain. Furthermore, S38151 administration (10 and 30 mg/kg) does not affect food intake, water intake, or body weight gain in MCHR1-deleted mice, demonstrating that its effects are linked to its interaction with MCH(1). These results validate MCH(1) as a target of interest in obesity. S38151 cannot progress to the clinical phase because it is still too poorly stable in vivo.
Authors:
Odile Della-Zuana; Valérie Audinot; Viviane Levenez; Alain Ktorza; Françoise Presse; Jean-Louis Nahon; Jean A Boutin
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Publication Detail:
Type:  Journal Article     Date:  2012-12-21
Journal Detail:
Title:  Frontiers in endocrinology     Volume:  3     ISSN:  1664-2392     ISO Abbreviation:  Front Endocrinol (Lausanne)     Publication Date:  2012  
Date Detail:
Created Date:  2012-12-25     Completed Date:  2012-12-26     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  101555782     Medline TA:  Front Endocrinol (Lausanne)     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  160     Citation Subset:  -    
Affiliation:
Maladies Métaboliques, Institut de Recherches SERVIER Suresnes, France.
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