Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size

Eur J Pharmacol. 2004 Aug 16;497(1):41-7. doi: 10.1016/j.ejphar.2004.06.027.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Eating / drug effects*
  • Feeding Behavior / drug effects*
  • Male
  • Motor Activity / drug effects
  • Naphthalenes / administration & dosage
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Obesity / drug therapy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Pituitary Hormone / antagonists & inhibitors*
  • Stereoisomerism
  • Time Factors

Substances

  • Biphenyl Compounds
  • Naphthalenes
  • Receptors, Pituitary Hormone
  • T-226296
  • melanin-concentrating hormone receptor