LSN2814617

LSN2814617 is an orally active, potent, brain-penetrant, and selective mGlu5 (metabotropic glutamate 5) positive allosteric modulator (PAM), with EC50 values of 52 nM (Human mGlu5) and 42 nM (rat mGlu5). LSN2814617 shows wake-promoting effect. LSN2814617 can be used for schizophrenia research[1].

Signaling Pathways >> GPCR/G Protein >> mGluR

Research Areas >> Neurological Disease

rat mGluR5:42 ± 9 nM (IC50)

human mGluR5:52 ± 21 nM (IC50)

LSN2814617 (1nM-10 μM) fails to elicit responses alone in rat cortical neurons, and evokes a concentration-dependent increase in the [Ca2+]i response in AV12 cells[1].

LSN2814617 (0.3-60 mg/kg, Orally, once) displays significant unbound brain exposure and dose-dependent occupancy of the mGlu5 receptor[1]. LSN2814617 (0-10 mg/kg, Orally, once) significantly modulates amphetamine-induced locomotor hyperactivity[1]. LSN2814617 (0-3 mg/kg, Orally, once) markedly increase wakefulness[1]. Animal Model: Male Lister Hooded rats (180-250 g, four to eight per cage)[1] Dosage: 0, 2.5, 5, and 10 mg/kg Administration: Orally, once, 60 min before amphetamine Result: Significantly modulated amphetamine hyperactivity, although a trend level decrease in hyperactivity was observed for the highest dose. At the end of the test session, from 75 to 120 min, the 10 mg/kg dose of LSN2814617 significantly increased amphetamine-induced hyperactivity. Animal Model: Adult male Wistar rats (approximately 270 g)[1] Dosage: 0, 0.3, 1, and 3 mg/kg Administration: Orally, once Result: Displayed dose-dependently increase in wakefulness immediately following oral administration; Produced 234 ± 16 min of increased wake for over 7 h in the case of 3 mg/kg. Produced dose-dependent reductions in both NREM and REM sleep.

[1]. Gilmour G, et al. In vitro characterisation of the novel positive allosteric modulators of the mGlu₅ receptor, LSN2463359 and LSN2814617, and their effects on sleep architecture and operant responding in the rat. Neuropharmacology. 2013 Jan;64:224-39.