Publication Date:
2002-07-27
Description:
D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients.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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- F31HG00201/HG/NHGRI NIH HHS/ -- P01DK056116/DK/NIDDK NIH HHS/ -- P01DK55819/DK/NIDDK NIH HHS/ -- R01MH061583/MH/NIMH NIH HHS/ -- R01MH44694/MH/NIMH NIH HHS/ -- R01MH61624/MH/NIMH NIH HHS/ -- R03TW01233/TW/FIC NIH HHS/ -- New York, N.Y. -- Science. 2002 Jul 26;297(5581):609-11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12142539" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Appetite Depressants/*pharmacology
;
Arcuate Nucleus of Hypothalamus/*drug effects/metabolism
;
Feeding Behavior/*drug effects
;
Fenfluramine/*pharmacology
;
Male
;
Melanocyte-Stimulating Hormones/pharmacology
;
Mice
;
Mice, Obese
;
Mice, Transgenic
;
Neurons/drug effects/metabolism
;
Paraventricular Hypothalamic Nucleus/drug effects/metabolism
;
Patch-Clamp Techniques
;
Pro-Opiomelanocortin/metabolism
;
Rats
;
Rats, Sprague-Dawley
;
Receptor, Melanocortin, Type 3
;
Receptor, Melanocortin, Type 4
;
Receptor, Serotonin, 5-HT2C
;
Receptors, Corticotropin/metabolism
;
Receptors, Serotonin/metabolism
;
Serotonin/metabolism
;
Serotonin Agents/pharmacology
;
alpha-MSH/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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