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Activation of Central Melanocortin Pathways by Fenfluramine

Science  26 Jul 2002:
Vol. 297, Issue 5581, pp. 609-611
DOI: 10.1126/science.1072327

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D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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

  • * To whom correspondence should be addressed. E-mail: jelmquis{at}caregroup.harvard.edu

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