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

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2006年 / 540卷 / 1-3期

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

页码：115 / 120

页数：6

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

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