Uses
JHU37160 is a potent and brain-penetrant DREADD agonist, with EC50s of 18.5nM and 0.2nM for hM3Dq and hM4Di DREADDs in HEK-293 cells, respectively. JHU37160 exhibits selective [3H]Clozapine displacement from DREADDs and not from other Clozapine-binding sites in mice brain tissue[1].
Biological Activity
JHU37160 (J60) is a potent DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) ligand (hM3Dq/hM4Di Ki = 1.9/3.6 nM using mouse brain tissue, 18.5/0.2 nM by celluar BRET assays) with ~25-fold improved affinity than C21 and high in vivo potency for CNS applications. J60 selectively competes against clozapine at DREADDs, but not other clozapine-binding sites in mouse brain tissue ex vivo (10 nM), increases hM3Dq-stimulated locomotion in TH-hM3Dq rats (0.01-0.3 mg/kg i.p.) and selectively inhibits locomotor activity of D1-hM3Dq and D1-hM4Di transgenic, but not wild-type, mice (0.01-1 mg/kg i.p.).
in vivo
JHU37160 (0.1 mg/kg; i.p.) exhibits high DREADD occupancy in mice and rats[1].
JHU37160 (0.01-1 mg/kg; i.p.) selectively inhibits locomotor activity in D1-hM3Dq and D1-hM4Di mice without any significant locomotor effects observed in WT mice[1].
References
[1] Bonaventura J, et, al. High-potency ligands for DREADD imaging and activation in rodents and monkeys. Nat Commun. 2019 Oct 11;10(1):4627. DOI:
10.1038/s41467-019-12236-z
![5H-Dibenzo[b,e][1,4]diazepine, 8-chloro-11-(4-ethyl-1-piperazinyl)-4-fluoro- Structure](https://www.chemicalbook.com/CAS/20210111/GIF/2369979-68-8.gif)
