Ampreloxetine hydrochloride (C09-1101-624)

Ampreloxetine (TD-9855) hydrochloride is an orally active and CNS-penetrant inhibitor of Norepinephrine transporter (NET) and Serotonin 5-HT uptake transporter (SERT), but not Dopamine transporter (DAT). Ampreloxetine hydrochloride binds norepinephrine transporters (NET) and serotonin transporters (SERT) with EC 50 values of 11.7 ng/mL and 50.8 ng/mL, respectively, in plasmaIn VivoAmpreloxetine hydrochloride (0.3-60 mg/kg; PO; single dose) is irrespective between plasma concentration and dose level in rat model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Rat Dosage: 0.3, 1, 5, 10, 30, and 60mg/kg Administration: PO; euthanized by decapitation at 0.5, 2, 4, 6, and 8 hr for 5mg/ kg dose level; 2 hr for 0.3, 1, 10, 30, and 60mg/kg dose levels Result: In the effect compartment PK/PD analysis for NET and SERT occupancy, the estimated EC 50 for occupancy was 11.7ng/mL for NET and 50.8ng/mL for SERT in rat spinal cords, and the projected human plasma EC 50 values were 5.5ng/mL for NET and 23.9ng/mL for SERT.IC50& Target:human Norepinephrine transporter 8.0 (pIC 50 ) human Serotonin transporter 8.6 (pIC 50 ) rat Norepinephrine transporter 7.9 (pIC 50 ) rat Serotonin transporter 8.9 (pIC 50 ). Molecular Formula: C18H19ClF3NO Molecular Weight: 357.8 PubChem CID: 46189894 Isomeric SMILES: C1CNCCC1C2=CC=CC=C2COC3=C(C=C(C=C3F)F)F.Cl