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- Title
Activation of central melanocortin pathways by fenfluramine.
- Authors
Heisler, Lora K; Cowley, Michael A; Tecott, Laurence H; Fan, Wei; Low, Malcolm J; Smart, James L; Rubinstein, Marcelo; Tatro, Jeffrey B; Marcus, Jacob N; Holstege, Henne; Lee, Charlotte E; Cone, Roger D; Elmquist, Joel K
- Abstract
D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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 anti-obesity treatments.
- Publication
Science (New York, N.Y.), 2002, Vol 297, Issue 5581, p609
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1072327