ML380 is a potent, subtype-selective, and brain-penetrant positive allosteric modulator (PAM) of M5 mAChR , with EC 50 s of 190 and 610 nM for human and rat M5 , respectively. ML380 exhibits moderate selectivity versus the M1 and M3 mAChR subtypes. ML380 could increase the affinity of ACh for the M5 mAChR
In Vitro
ML380 (0.01 nM-100 μM) robustly stimulates inositol phosphate (IP) accumulation and Ca 2+ mobilization in CHO-hM 5 cells, with pEC 50 s of 5.33 and 5.71, respectively. ML380 (0.01-30 μM) increases the ACh-stimulated IP accumulation and Ca 2+ mobilization in CHO-hM 5 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ML380 (1 mg/kg; i.v.) displays high clearance (66 mL/min/kg), a moderate volume of distribution (1.6 L/kg), and a short half-life (t 1/2 , 22 min) in rats . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
