MCH1R (melanin-concentrating hormone 1 receptor) is one of the melanin-concentrating hormone receptors found in all mammals. What’s more, The protein encoded by this gene, a member of the G protein-coupled receptor family 1, is an integral plasma membrane protein that binds melanin-concentrating hormone. Besides, MCH1 has several functions including the regulation of appetite and stress, anxiety, and depression.

ATC0175 is a potent, selective, and orally active MCH1R antagonist. Besides, ATC0175 is also a noncompetitive MCH1R antagonist with IC₅₀ values of 13.5, >10000 nM for MCH1R, and MCH2R, respectively. Besides, This compound shows a high affinity for 5-HT2B and 5-HT1A with IC₅₀ values of 9.66 and 16.9 nM respectively.

ATC0175 has the potential for the research of depression and/or anxiety disorders.

ATC0175 exhibits anxiolytic effects in numerous animal models of anxiety including the elevated plus-maze test, social interaction test, stress-induced hyperthermia and maternal separation-induced vocalization. What’s more, ATC0175 significantly reversed swim stress-induced anxiety in the elevated plus-maze test in rats and stress-induced hyperthermia in mice. In addition, ATC0175 significantly increases social interaction between unfamiliar rats and reduces separation-induced vocalizations in guinea pig pups.

ATC0175 also exhibits antidepressant effects. What’s more, ATC0175 significantly increases swimming performance without altering climbing behavior. Besides, ATC0175 shows potent oral activity in animal models. Moreover, ATC0175 (1, 3, 10 mg/kg; p.o.) significantly and dose-dependently reduces immobility time, indicating antidepressant-like potential. Additionally, ATC0175 (30 mg/kg) did not affect spontaneous locomotor activity, or haloperidol-induced sleeping time and did not impair rotarod performance. Furthermore, ATC0175 does not cause unwanted side effects on the central nervous system (CNS). In addition, ATC0175 was well tolerated in rat repeated toxicity studies and had no genotoxic liability.

In conclusion, ATC0175 is a potent, selective and orally active MCH1R antagonist with IC₅₀ values of 13.5, >10000 nM for MCH1R, and MCH2R, respectively. Besides, ATC0175 shows antidepressant effects and anxiolytic effects in animal models.

Reference

[1] Chaki S, et al. CNS Drug Rev. 2005 Winter;11(4):341-52.