An Indirect Screen for Brain Uptake of 1,2-Diarylethane Melanocortin 4 Receptor Antagonists in Rats

2007 ◽  
Vol 1 (3) ◽  
pp. 195-198
Author(s):  
Wei Yin ◽  
Liang-Shang Gan ◽  
Jing-Tao Wu ◽  
Suresh K. Balani ◽  
Hua Yang ◽  
...  
Keyword(s):  
Brain Uptake ◽  
Receptor Antagonists ◽  
Melanocortin 4 Receptor

Efficacy of orally available selective melanocortin-4 receptor antagonists in a murine model of cancer cachexia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20668-e20668
Author(s):  
R. Dallmann ◽  
P. Weyermann ◽  
J. P. Magyar ◽  
C. Anklin ◽  
M. Hufschmid ◽  
...  
Keyword(s):  
Food Intake ◽  
Oral Administration ◽  
Animal Studies ◽  
Cancer Cachexia ◽  
Receptor Antagonists ◽  
Melanocortin 4 Receptor ◽  
Increase Food Intake ◽  
Life Threatening ◽  
Anorexigenic Peptide ◽  
Orally Active

e20668 Background: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC)-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP), the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. Methods: Two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier were studied. Specifically, the influence on food intake in healthy mice, and effects in the murine C26 cancer-cachexia model were investigated. Results: Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation) of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. Conclusions: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. In the light of patient care, orally active compounds might offer a considerable advantage for the treatment of cancer cachexia. [Table: see text]

Pharmacological and pharmacokinetic characterization of 2-piperazine-α-isopropyl benzylamine derivatives as melanocortin-4 receptor antagonists

2008 ◽  
Vol 16 (10) ◽  
pp. 5606-5618 ◽  
Author(s):  
Chen Chen ◽  
Fabio C. Tucci ◽  
Wanlong Jiang ◽  
Joe A. Tran ◽  
Beth A. Fleck ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Melanocortin 4 Receptor

scholarly journals Orally Available Selective Melanocortin-4 Receptor Antagonists Stimulate Food Intake and Reduce Cancer-Induced Cachexia in Mice

PLoS ONE ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. e4774 ◽  
Author(s):  
Philipp Weyermann ◽  
Robert Dallmann ◽  
Josef Magyar ◽  
Corinne Anklin ◽  
Martina Hufschmid ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonists ◽  
Melanocortin 4 Receptor
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