Nature Medicine8, 825 - 830 (2002)
Published online: 15 July 2002; | doi:10.1038/nm741
There is a Corrigendum (September 2002) associated with this Article.
Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist
Beth Borowsky, Margaret M. Durkin, Kristine Ogozalek, Mohammad R. Marzabadi, John DeLeon, Rainer Heurich, Harvey Lichtblau, Zoya Shaposhnik, Irena Daniewska, Thomas P. Blackburn, Theresa A. Branchek, Christophe Gerald, Pierre J. Vaysse
& Carlos Forray
Synaptic Pharmaceutical Corporation, Paramus, New Jersey, USA
Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight. Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. In addition, after mapping the binding sites for [3H]SNAP-7941 in rat brain, we evaluated its effects in a series of behavioral models. SNAP-7941 produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may be useful not only in the management of obesity but also as a treatment for depression and/or anxiety.
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