ATC0175: an orally active melanin-concentrating hormone receptor 1 antagonist for the potential treatment of depression and anxiety.

CNS Drug Reviews
Shigeyuki ChakiYoshinori Sekiguchi

Abstract

Melanin-concentrating hormone (MCH) has been implicated in a variety of physiological events. Recent studies clearly suggest that MCH plays an important role in the regulation of stress and emotion. To date, two receptor subtypes of MCH (MCH1R and MCH2R) have been identified. MCH1R has been suggested to mediate most of the physiological functions of MCH. Recently, we synthesized an orally active, nonpeptidic antagonist of MCH1R, N-(cis-4-{[4-(dimethylamino)quinazolin-2-yl]amino}cyclohexyl)-3,4-difluorobenzamide hydrochloride (ATC0175). This compound is a potent antagonist with a high affinity for MCH1R and additional affinities for 5-HT1A and 5-HT2B receptors. The receptor binding and the functional assay (MCH-induced increase in [Ca2+]i) indicated that ATC0175 is a noncompetitive antagonist at MCH1Rs. ATC0175 exhibited anxiolytic effects in numerous animal models of anxiety including the elevated plus-maze test, social interaction test, stress-induced hyperthermia and maternal separation-induced vocalization. Like with other stress-related peptide receptor antagonists, such as antagonists of corticotropin-releasing factor or vasopressin V1b receptor antagonists, anxiolytic effects of ATC0175 were more pronounced in models cont...Continue Reading

References

May 8, 1992·The Journal of Comparative Neurology·J C BittencourtP E Sawchenko
Jan 1, 1991·Pharmacology, Biochemistry, and Behavior·K Njung'e, S L Handley
Jan 1, 1999·Nature·M ShimadaE Maratos-Flier
Mar 4, 2000·Peptides·M E MonzonS R de Barioglio
Feb 13, 2001·The Journal of Clinical Investigation·D S LudwigE Maratos-Flier
May 23, 2001·The Journal of Comparative Neurology·Y SaitoO Civelli
Sep 15, 2001·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·M J MillanA Dekeyne
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Donald J MarshSu Qian
May 15, 2002·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A D SmithM J Zigmond
May 15, 2002·Trends in Pharmacological Sciences·John F CryanIrwin Lucki
Aug 31, 2002·Psychopharmacology·Franco BorsiniDonatella Marazziti
Sep 13, 2002·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Robert C SmithAngelica Kloos
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·Guy GriebelRégis Steinberg
Jan 28, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniel G SmithDonald R Gehlert
Jan 29, 2005·The Journal of Pharmacology and Experimental Therapeutics·Shigeyuki ChakiWilliam Thomsen
Mar 18, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dan GeorgescuRalph J DiLeone

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