PMID: 11907191Mar 22, 2002Paper

4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders

The Journal of Pharmacology and Experimental Therapeutics
Guy GriebelPhilippe Soubrié

Abstract

The present study investigated the effects of the novel corticotrophin-releasing factor (CRF)(1) receptor antagonist 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A) in a variety of rodent models of anxiety, including conflict procedures (punished drinking and four-plate), exploration models (elevated plus-maze and light/dark), a fear/anxiety defense test battery, and several procedures based on stress-induced changes in physiological (isolation-induced hyperthermia and tail pinch-induced cortical norepinephrine release) or behavioral (social defeat-induced anxiety, maternal separation-induced vocalization) parameters. Moreover, the effects of SSR125543A were investigated in acute (forced swimming) and chronic (chronic mild stress; CMS) models of depression. SSR125543A and the CRF(1) receptor antagonist antalarmin displayed limited efficacy in exploration-based anxiety models. In contrast, both compounds produced clear-cut anxiolytic-like activity in models involving inescapable stress, including the conflict procedures, the social defeat-induced anxiety paradigm and the defense test battery (3-30 mg/kg i.p. or p.o...Continue Reading

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Citations

Oct 4, 2005·Médecine sciences : M/S·Elisabeth MocaërChristian de Bodinat
Apr 27, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jeanne StemmelinGuy Griebel
Apr 5, 2007·Neurochemical Research·Eleni PaizanisLaurence Lanfumey
Mar 4, 2009·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Siegfried Kasper, Michel Hamon
Aug 14, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Arati S KreibichJulie A Blendy
Jan 12, 2010·The International Journal of Neuropsychopharmacology·Severine FarleyEleni T Tzavara
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Apr 22, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Andrzej WróbelJarosław Dudka
Feb 22, 2003·CNS Drug Reviews·Patricia A SeymourDavid W Schulz
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