ATC0065 is a selective and potent antagonist of the melanin-concentrating hormone receptor 1 (MCH1) with IC50 of 15.7 nM. This component also displays affinity for 5-HT1A and 5-HT2B receptors with IC50 of 62.9nM and 266 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 assay, ATC0065 bounds with high affinity to the MCH-R1 with IC50 value of 16 nMand showed good metabolic stability in liver microsomes isolated from human and rat 1.
In rodents, ATC0065 is potent and orally active MCHR1 antagonists with anxiolytic and antidepressant activity. ATC0065 treatmetn significantly reversed swim stress-induced anxiety in the stress-induced hyperthermia in mice and elevated plus-maze test in rats2. However, ATC0065 did not affect spontaneous locomotor activity or rotarod performance in rats 2.
References:
1. Kanuma K, Omodera K, Nishiguchi M, et al. Identification of 4-amino-2-cyclohexylaminoquinazolines as metabolically stable melanin-concentrating hormone receptor 1 antagonists. Bioorganic & medicinal chemistry. 2006;14(10):3307-3319.
2. Chaki S, Funakoshi T, Hirota-Okuno S, et al. Anxiolytic- and antidepressant-like profile of ATC0065 and ATC0175: nonpeptidic and orally active melanin-concentrating hormone receptor 1 antagonists. The Journal of pharmacology and experimental therapeutics. 2005;313(2):831-839.