Velneperit

Velneperit (S-2367) is an orally active neuropeptide Y (NPY) Y5 receptor antagonist that can penetrate the blood-brain barrier. Velneperit inhibits the appetite-stimulating and metabolism-inhibiting effects mediated by NPY. Velneperit selectively improves diet-induced obesity in mice. Velneperit enhances the expression of fear acutely by removing the inhibition of CeA Drd2 neurons. Velneperit can be used for the study of obesity^[1][2][3]. In Vivo:Velneperit (30-100 mg/kg, p.o., once daily for 2 weeks) significantly inhibits weight gain caused by moderate high-fat (MHF) diet in mice, and is ineffective for mice on a regular diet and those with genetic obesity^[1].
Velneperit (100 mg/kg, p.o., single dose) achieves high brain Y5 receptor occupancy rates of 80-90% and maintains sustained plasma concentrations at elevated levels for up to 15 hours in mice and rats^[1].
Velneperit (100 mg/kg, i.p., single dose) rapidly and acutely enhances the fear expression in mice, providing evidence that NPY5R is the endogenous inhibitory receptor of Drd2 neurons^[2].