Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety.
Eur J Pharmacol
; 540(1-3): 115-20, 2006 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-16765941
ABSTRACT
The aim of this study was to validate melanin-concentrating hormone (MCH)-1 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anxiety
/
Piperidines
/
Pyrimidines
/
Biphenyl Compounds
/
Receptors, Somatostatin
/
Depressive Disorder
/
Naphthalenes
Type of study:
Guideline
Limits:
Animals
Language:
En
Journal:
Eur J Pharmacol
Year:
2006
Document type:
Article
Affiliation country:
Estados Unidos