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

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.

• Authors: Timothy J Kowalski, Constance Farley, Mary E Cohen-Williams, Geoffrey Varty, Brian D Spar
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 497 Issue 1 Pg. 41-7 (Aug 16 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15321733 (Publication Type: Comparative Study, Journal Article)

Chemical References

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

Topics

• 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