Activation of Central Melanocortin Pathways by Fenfluramine

HEISLER LK, COWLEY MA, TECOTT LH, FAN W, LOW MJ, SMART JL, RUBINSTEIN M, TATRO J, HOLSTEGE H, LEE C, CONE R, ELMQUIST J

SCIENCE

AMER ASSOC ADVANCEMENT SCIENCE

Año: 2002 vol. 297 p. 609 - 611

0036-8075

D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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