title: Methylnaltrexone reduced body weight gain in ob/ob mice.
abstract: OBJECTIVE
  Opioids may function to regulate food intake and body weight, an activity that could be predominantly centrally mediated. In this study, the authors evaluated the effects of a peripherally acting opioid receptor antagonist, methylnaltrexone, on weight changes in adult obese ob/ob mice.
  
  
  RESULTS
  After a 12-day treatment with naloxone 0.3 mg/kg, weight was reduced from 63.7 +/- 1.1 g in the control group to 59.2 +/- 0.9 g in the naloxone group (p < 0.05). After a 12-day treatment with methylnaltrexone 3.0 mg/kg, weight increase completely ceased. The body weight was 63.9 +/- 1.0 g in the control group when compared with 55.9 +/- 1.2 g in the drug group (p < 0.01). The effect of methylnaltrexone (1.0 mg to 3.0 mg/kg) on weight changes was dose-dependent (p < 0.01). Methylnaltrexone significantly reduced daily food intake (p < 0.05), but did not affect body temperature and energy expenditure. Using HPLC analysis, no detectable naltrexone levels were found in association with methylnaltrexone administration. Whether the observed methylnaltrexone effects are primarily related to the antagonism of endorphinergic system remains to be investigated.
  
  
  CONCLUSIONS
  Our results suggest that the peripheral opioid mechanism contributes to modulating food ingestion and methylnaltrexone may have clinical importance in obesity management.
authors.affiliation: Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Illinois, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Anoja
authors.initials: A
authors.lastname: Attele
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone