HS-014 is an antagonist of melanocortin receptor 4 (MC4R; Ki = 3.16 nM).1 It is selective for MC4R over MC1R, MC3R, and MC5R (Kis = 108, 54.4, and 694 nM, respectively). HS-014 inhibits cAMP accumulation induced by α-melanocyte-stimulating hormone (α-MSH) in COS-1 cells expressing MC4R in a concentration-dependent manner. It increases food intake in free-feeding rats when administered intracerebroventricularly at doses of 1 or 3 nmol/animal.2 Intracerebroventricular administration of HS-014 (0.008 ng/animal) increases the latency to tail withdrawal in the tail-flick test, as well as inhibits morphine withdrawal-induced decreases in the latency to tail withdrawal in the tail-flick test, in rats.3 It reduces immobility time in the forced swim test, as well as increases time in the open area and reduces the number of droppings in an open field test, in rats when administered at a dose of 100 ?g/animal.4
References:
[1]. Schi?th, H.B., Mutulis, F., Muceniece, R., et al.Discovery of novel melanocortin4 receptor selective MSH analoguesBr. J. Pharmacol.124(1)75-82(1998).
[2]. Kask, A., R?go, L., Mutulis, F., et al.Selective antagonist for the melanocortin 4 receptor (HS014) increases food intake in free-feeding ratsBiochem. Biophys. Res. Commun.245(1)90-93(1998).
[3]. Kalange, A.S., Kokare, D.M., Singru, P.S., et al.Central administration of selective melanocortin 4 receptor antagonist HS014 prevents morphine tolerance and withdrawal hyperalgesiaBrain Res.118110-20(2007).
[4]. Serova, L.I., Laukova, M., Alaluf, L.G., et al.Intranasal infusion of melanocortin receptor four (MC4R) antagonist to rats ameliorates development of depression and anxiety related symptoms induced by single prolonged stressBehav. Brain Res.250139-147(2013).