Activation of central melanocortin pathways by fenfluramine

Lora K. Heisler, Michael A. Cowley, Laurence H. Tecott, Wei Fan, Malcolm J. Low, James L. Smart, Marcelo Rubinstein, Jeffrey B. Tatro, Jacob N. Marcus, Henne Holstege, Charlotte E. Lee, Roger D. Cone, Joel K. Elmquist

Research output: Contribution to journalArticle

382 Scopus citations

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D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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 antiobesity treatments.

Original languageEnglish (US)
Pages (from-to)609-611
Number of pages3
JournalScience
Volume297
Issue number5581
DOIs
StatePublished - Jul 26 2002

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    Heisler, L. K., Cowley, M. A., Tecott, L. H., Fan, W., Low, M. J., Smart, J. L., Rubinstein, M., Tatro, J. B., Marcus, J. N., Holstege, H., Lee, C. E., Cone, R. D., & Elmquist, J. K. (2002). Activation of central melanocortin pathways by fenfluramine. Science, 297(5581), 609-611. https://doi.org/10.1126/science.1072327