Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety

被引:40
作者
Basso, Ana M. [1 ]
Bratcher, Natalie A. [1 ]
Gallagher, Kelly B. [1 ]
Cowart, Marlon D. [1 ]
Zhao, Chen [1 ]
Sun, Minghua [1 ]
Esbenshade, Timothy A. [1 ]
Brune, Michael E. [1 ]
Fox, Gerard B. [1 ]
Schmidt, Martin [1 ]
Collins, Christine A. [1 ]
SouerS, Andrew J. [1 ]
Iyengar, Rajesh [1 ]
Vasudevan, Anil [1 ]
Kyrn, Philip R. [1 ]
Hancock, Arthur A. [1 ]
Rueter, Lynne E. [1 ]
机构
[1] Abbott Labs, Abbott Pk, IL 60064 USA
关键词
MCH-1 receptor antagonists; depression; anxiety; (rat); (mouse);
D O I
10.1016/j.ejphar.2006.04.043
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The aim of this study was to validate melanin-concentrating hormone (MCH)- I receptor antagonism as a potential treatment of mood disorders. We attempted to replicate the effects previously reported with SNAP-7941 and expanded the investigation to three other orally bioavailable MCH-1 receptor antagonists with good brain penetration. SNAP-7941 (3-30 mg/kg, i.p.) and T-226296 (5-60 mg/kg, p.o.) (+/- racemate), were evaluated in the rat forced swim and mouse tail suspension tests. (+)SNAP-7941 (3-10 mg/kg, p.o.) was also tested in a modified 5-min rat forced swim protocol as previously reported. A-665798 (3-30 mg/kg, p.o.) and A-777903 (3-30 mg/kg, p.o.) were tested in mouse tail suspension and rat Vogel tests. None of the compounds showed meaningful efficacy in the paradigms tested. The lack of efficacy with four structurally different MCH-1 receptor antagonists does not support a role for therapeutic treatment of depression/anxiety via this mechanism of action. (c) 2006 Elsevier B.V All rights reserved.
引用
收藏
页码:115 / 120
页数:6
相关论文
共 17 条
[1]   Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist [J].
Borowsky, B ;
Durkin, MM ;
Ogozalek, K ;
Marzabadi, MR ;
DeLeon, J ;
Heurich, R ;
Lichtblau, H ;
Shaposhnik, Z ;
Daniewska, I ;
Blackburn, TP ;
Branchek, TA ;
Gerald, C ;
Vaysse, PJ ;
Forray, C .
NATURE MEDICINE, 2002, 8 (08) :825-830
[2]   Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: Nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists [J].
Chaki, S ;
Funakoshi, T ;
Hirota-Okuno, S ;
Nishiguchi, M ;
Shimazaki, T ;
Iijima, M ;
Grottick, AJ ;
Kanuma, K ;
Omodera, K ;
Sekiguchi, Y ;
Okuyama, S ;
Tran, TA ;
Semple, G ;
Thomsen, W .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (02) :831-839
[3]   ACTIVE BEHAVIORS IN THE RAT FORCED SWIMMING TEST DIFFERENTIALLY PRODUCED BY SEROTONERGIC AND NORADRENERGIC ANTIDEPRESSANTS [J].
DETKE, MJ ;
RICKELS, M ;
LUCKI, I .
PSYCHOPHARMACOLOGY, 1995, 121 (01) :66-72
[4]   The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus Accumbens to modulate feeding Behavior and forced-swim performance [J].
Georgescu, D ;
Sears, RM ;
Hommel, JD ;
Barrot, M ;
Bolaños, CA ;
Marsh, DJ ;
Bednarek, MA ;
Bibb, JA ;
Maratos-Flier, E ;
Nestler, EJ ;
DiLeone, RJ .
JOURNAL OF NEUROSCIENCE, 2005, 25 (11) :2933-2940
[5]   Behavioral effects of alpha-MSH and MCH after central administration in the female rat [J].
Gonzalez, MI ;
Vaziri, S ;
Wilson, CA .
PEPTIDES, 1996, 17 (01) :171-177
[6]   Melanin-concentrating hormone functions in the nervous system: food intake and stress [J].
Hervieu, G .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2003, 7 (04) :495-511
[7]   Behavioural analysis of melanin-concentrating hormone in rats: evidence for orexigenic and anxiolytic properties [J].
Kela, J ;
Salmi, P ;
Rimondini-Giorgini, R ;
Heilig, M ;
Wahlestedt, C .
REGULATORY PEPTIDES, 2003, 114 (2-3) :109-114
[8]   Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: Further evidence for a stimulatory role in the adrenal axis via SLC-1 [J].
Kennedy, AR ;
Todd, JF ;
Dhillo, WS ;
Seal, LJ ;
Ghatei, MA ;
O'Toole, CP ;
Jones, M ;
Witty, D ;
Winborne, K ;
Riley, G ;
Hervieu, G ;
Wilson, S ;
Bloom, SR .
JOURNAL OF NEUROENDOCRINOLOGY, 2003, 15 (03) :268-272
[9]   Discovery and characterization of aminopiperidinecoumarin melanin concentrating hormone receptor 1 antagonists [J].
Kym, PR ;
Iyengar, R ;
Souers, AJ ;
Lynch, JK ;
Judd, AS ;
Gao, J ;
Freeman, J ;
Mulhern, M ;
Zhao, G ;
Vasudevan, A ;
Wodka, D ;
Blackburn, C ;
Brown, J ;
Che, JL ;
Cullis, C ;
Lai, SJ ;
LaMarche, MJ ;
Marsilje, T ;
Roses, J ;
Sells, T ;
Geddes, B ;
Govek, E ;
Patane, M ;
Fry, D ;
Dayton, BD ;
Brodjian, S ;
Falls, D ;
Brune, M ;
Bush, E ;
Shapiro, R ;
Knourek-Segel, V ;
Fey, T ;
McDowell, C ;
Reinhart, GA ;
Preusser, LC ;
Marsh, K ;
Hernandez, L ;
Sham, HL ;
Collins, CA .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (19) :5888-5891
[10]   Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus [J].
Ludwig, DS ;
Mountjoy, KG ;
Tatro, JB ;
Gillette, JA ;
Frederich, RC ;
Flier, JS ;
Maratos-Flier, E .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1998, 274 (04) :E627-E633