Activation of central melanocortin pathways by fenfluramine

D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs to prevent and treat obesity. Through a combination of functional neuroanatomy, feeding and electrophysiology studies in rodents, we show that d-FEN-induced anorexia requires activation of central nervous system melanocortin pathways. These results provide a mechanistic explanation of d-FEN's anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to be effective and more selective antiobesity treatments.Fil: Heisler, Lora K.. Harvard Medical School; Estados UnidosFil: Cowley, Michael A.. Oregon Health and Science University; Estados UnidosFil: Tecott, Laurence H.. University of California; Estados UnidosFil: Fan, Wei. Oregon Health and Science University; Estados UnidosFil: Low, Malcolm J.. Oregon Health and Science University; Estados UnidosFil: Smart, James L.. Oregon Health and Science University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Tatro, Jeffrey B.. Tufts University School of Medicine; Estados UnidosFil: Marcus, Jacob N.. Harvard Medical School; Estados UnidosFil: Holstege, Henne. Harvard Medical School; Estados UnidosFil: Lee, Charlotte E.. Harvard Medical School; Estados UnidosFil: Cone, Roger D.. Oregon Health and Science University; Estados UnidosFil: Elmquist, Joel K.. Harvard Medical School; Estados Unido