Piromelatine is an agonist of melatonin MT1/MT2 receptors, 5-HT1A and 5-HT1D, and an antagonist of 5-HT2B.Piromelatine has antinociceptive activity with inhibitory effects on P2X3, TRPV1, and Nav1.7 channels, and can be used in studies of sleep-promoting, pain-relieving, anti-neurodegenerative, and antidepressant diseases. diseases, and can be used to improve memory deficits associated with chronic mild stress-induced lack of pleasure in rats.

Piromelatine (Neu-P11) has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFSD) rats. The objective of this study was to investigate the effects of piromelatine on insulin sensitivity in sleep-restricted rats. Sleep restriction was established by rotating cages intermittently for 20h thereby sleeping time of rats was limited to 4 hours per day. During 8 days of sleep restriction, rats were injected intraperitoneally with piromelatine (20mg/kg), melatonin (5mg/kg), or a vehicle. The results showed that sleep restriction increased plasma glucose, fasting insulin, total cholesterol (TC), triglycerides (TG), and oxidative stress markers while HDL-cholesterol (HDL-C) level and glucose tolerance were decreased. However, under piromelatine or melatonin treatment, the levels of plasma glucose, TG, and TC decreased and HDL-C, glucose tolerance, and antioxidative potency increased when compared with the vehicle-treated group. Piromelatine could regulate metabolic profiles and insulin sensitivity, and attenuate insulin resistance induced by sleep restriction.[3]