Document Detail

Agonist diversity in 5-HT(2C) receptor-mediated weight control in rats.
MedLine Citation:
PMID:  15719229     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Food intake and energy expenditure are the two main determinants of body weight. Given that 5-HT(2C) receptor agonists are reported to have effects on both energy expenditure and food intake, this strongly suggests that 5-HT(2C) receptor agonists have excellent potential for development as antiobesitiy drugs. One important issue in antiobesity drug development is whether the effects of the compound are maintained during chronic drug treatment. OBJECTIVES: The purpose of the present study was to investigate the effect of repeated oral administration of three 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP), d(S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine (RO60-0175) and (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), on food intake and energy expenditure in rats. RESULTS: In the food intake study, mCPP, RO60-0175 and YM348 decreased food intake in a dose-dependent manner on day 1 of administration. On day 14 of repeated administration, the hypophagic effect of YM348 was lost and that of mCPP was reduced. In contrast, the hypophagic effect of RO60-0175 was maintained even after repeated administration. The hypophagic effects of all agonists were significantly inhibited by a 5-HT(2C) receptor antagonist, SB242084. In contrast to the hypophagic effects, no drug tolerance developed with respect to the hyperthermic effects of mCPP, RO60-0175, and YM348. The hyperthermic effects of these drugs were also inhibited by SB242084. CONCLUSIONS: Together, the difference between compounds in their hypophagic effects and the similarity in their hyperthermic effects suggest a diversity in agonists in 5-HT(2C) receptor-mediated weight control in rats.
Aska Hayashi; Masanori Suzuki; Masao Sasamata; Keiji Miyata
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Publication Detail:
Type:  Journal Article     Date:  2004-10-21
Journal Detail:
Title:  Psychopharmacology     Volume:  178     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-18     Completed Date:  2005-09-12     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  241-9     Citation Subset:  IM    
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
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MeSH Terms
Administration, Oral
Aminopyridines / pharmacology
Appetite Depressants / pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Energy Metabolism / drug effects*
Ethylamines / pharmacology
Feeding Behavior / drug effects*
Indoles / pharmacology
Piperazines / pharmacology
Rats, Wistar
Receptor, Serotonin, 5-HT2C / agonists*
Weight Loss / drug effects*
Reg. No./Substance:
0/Aminopyridines; 0/Appetite Depressants; 0/Ethylamines; 0/Indazoles; 0/Indoles; 0/Piperazines; 0/Receptor, Serotonin, 5-HT2C; 0/Ro 60-0175; 0/SB 242084; 0/YM348; 6640-24-0/1-(3-chlorophenyl)piperazine

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

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