Activation of central melanocortin pathways by fenfluramine

LK Heisler, MA Cowley, LH Tecott, W Fan, MJ Low… - Science, 2002 - science.org
LK Heisler, MA Cowley, LH Tecott, W Fan, MJ Low, JL Smart, M Rubinstein, JB Tatro…
Science, 2002science.org
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weight loss drugs, but was withdrawn from clinical use because of reports of cardiac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 …
D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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.
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