LSN2814617 is an orally active, potent, brain-penetrant, and selective mGlu 5 (metabotropic glutamate 5) positive allosteric modulator (PAM), with EC 50 values of 52 nM (Human mGlu5) and 42 nM (rat mGlu5). In vivo EEG studies demonstrated that LSN2463359 has marked wake-promoting properties with minimal rebound hypersomnolence, and it can be used for schizophrenia research [1].

mGluR5 (rat):42 ± 9 nM, mGluR5 (human):52 ± 21 nM

LSN2814617 (1nM-10 μM) does not elicit responses in rat cortical neurons but induces a concentration-dependent increase in the [Ca2+]i response in AV12 cells [1].

Administered orally in doses ranging from 0.3 to 60 mg/kg, LSN2814617 demonstrates significant unbound brain exposure and dose-dependent mGlu5 receptor occupancy, as well as markedly modulating amphetamine-induced locomotor hyperactivity in doses up to 10 mg/kg. In doses up to 3 mg/kg, it notably increases wakefulness. In the study involving male Lister Hooded rats (180-250 g, housed four to eight per cage), doses of 0, 2.5, 5, and 10 mg/kg of LSN2814617, given orally 60 minutes before amphetamine exposure, significantly modulated amphetamine hyperactivity. Notably, the highest dose displayed a trend towards reduced hyperactivity. However, from 75 to 120 minutes into the test session, the 10 mg/kg dose significantly increased amphetamine-induced hyperactivity. In adult male Wistar rats (approximately 270 g), doses of 0, 0.3, 1, and 3 mg/kg resulted in a dose-dependent increase in wakefulness immediately after administration, with the 3 mg/kg dose yielding 234 ± 16 minutes of increased wakefulness over 7 hours and also reducing both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep.