| Description | 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 but little in the way of rebound hypersomnolence. LSN2814617 can be used for schizophrenia research [1]. |
| In vitro | LSN2814617 (1nM-10 μM) fails to elicit responses alone in rat cortical neurons, and causes a concentration-dependent increase in the [Ca2+]i response in AV12 cells [1]. |
| In vivo | LSN2814617 (0.3-60 mg/kg, Orally, once) shows 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) significantly 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. |
| Synonyms | LSN-2814617, LSN 2814617 |
| molecular weight | 341.38 |
| Molecular formula | C18H20FN5O |
| CAS | 1313498-17-7 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Loomis S, McCarthy A, Baxter C, Kellett DO, Edgar DM, Tricklebank M, Gilmour G. Distinct pro-vigilant profile induced in rats by the mGluR5 potentiator LSN2814617. Psychopharmacology (Berl). 2015 Nov;232(21-22):3977-89. doi: 10.1007/s00213-015-3936-8. PubMed PMID: 25902875; PubMed Central PMCID: PMC4600478. 2. Ahnaou A, Langlois X, Steckler T, Bartolome-Nebreda JM, Drinkenburg WH. Negative versus positive allosteric modulation of metabotropic glutamate receptors (mGluR5): indices for potential pro-cognitive drug properties based on EEG network oscillations and sleep-wake organization in rats. Psychopharmacology (Berl). 2015 Mar;232(6):1107-22. doi: 10.1007/s00213-014-3746-4. PubMed PMID: 25323624. 3. Gilmour G, Broad LM, Wafford KA, Britton T, Colvin EM, Fivush A, Gastambide F, Getman B, Heinz BA, McCarthy AP, Prieto L, Shanks E, Smith JW, Taboada L, Edgar DM, Tricklebank MD. 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. doi: 10.1016/j.neuropharm.2012.07.030. PubMed PMID: 22884720. |