A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally.
Melanocortin receptors are considered promising candidates for the treatment of behavioral and metabolic disorders ranging from obesity to anorexia and cachexia. These experiments examined the response of mice to peripheral injections of two compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of melanocortin-3 and melanocortin-4 receptors (Mc3r and Mc4r). PG946 is a derivative of a hybrid of alpha- and beta-MSH, and is a moderately selective Mc3r antagonist. SHU9119 increases food intake when administered intracerebroventricularly but is without effect when injected into the periphery. In contrast, PG932 was found to be highly effective at stimulating food intake when administered peripherally by intraperitoneal injection. The orexigenic effect of PG932 required functional Mc4r, suggesting that inhibition of this receptor is involved in the stimulation of food intake. PG946 did not significantly affect on feeding behavior. PG932 is thus a useful new compound for studies examining the regulation of appetite and energy balance, and may also prove useful for the treatment of cachectic conditions.
Neuropeptides Laboratory, Pennington Biomedical Research Center, Lousiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Gregory M
GM
Sutton
M
M
Josephine Babin
Xuyuan
X
Gu
Victor J
VJ
Hruby
Andrew A
AA
Butler
D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000188:drug therapy; D004244:Dizziness / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000494:pharmacology*; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors*; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000502:physiology
D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C527847:acetyl-norleucyl-cyclo(aspartyl-prolyl-2-naphthylalanyl-arginyl-tryptophyl-lysyl)-prolyl-valyinamide; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones