snap7941 and Depressive-Disorder

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.

Topics: Analysis of Variance; Animals; Anxiety; Benzopyrans; Biphenyl Compounds; Conflict, Psychological; Depressive Disorder; Disease Models, Animal; Hindlimb Suspension; Indazoles; Male; Mice; Mice, Inbred BALB C; Motor Activity; Naphthalenes; Piperidines; Pyrimidines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Somatostatin; Swimming