ATC0175 hydrochloride is a potent, selective and orally active antagonist of melanin-concentrating hormone receptor 1 (MCH1) with IC50 of 13 nM for MCH1. It was also shown to have affinity for 5-HT2B and 5-HT1A receptors with IC50 of 9.66 nM and 16.9 nM respectively.

Melanin-concentrating hormone receptor (MCH1), a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein which binds melanin-concentrating hormone. The protein can inhibit cAMP accumulation and stimulate intracellular calcium flux, and is probably involved in the neuronal regulation of food consumption.

In vitro, assays showed that this compound is a potent antagonist with a high affinity for MCH1R. The receptor binding and the functional assay (MCH-induced increase in [Ca2+]) indicated that ATC0175 is a noncompetitive antagonist at MCH1Rs 1.

In vivo, ATC0175 displayed anxiolytic effects in numerous animal models of anxiety including the social interaction test, elevated plus-maze test, maternal separation-induced vocalization and stress-induced hyperthermia. In addition, ATC0175 treatment also exhibited antidepressant effects in the forced swimming test 2.

References:
1.  Semple G, Tran TA, Kramer B, et al. Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. Bioorganic & medicinal chemistry letters. 2009;19(21):6166-6171.
2.   Chaki S, Yamaguchi J, Yamada H, et al. ATC0175: an orally active melanin-concentrating hormone receptor 1 antagonist for the potential treatment of depression and anxiety. CNS drug reviews. 2005;11(4):341-352.