Intermediate

Product NameIntermediate
CAS1227056-87-2
MFC18H18F3NO.ClH
MW357.8
EINECS
MOL File1227056-87-2.mol

Chemical Properties

form	Solid
color	White to off-white

Usage And Synthesis

Uses

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 EC50 values of 11.7 ng/mL and 50.8 ng/mL, respectively, in plasma[1].

in vivo

Ampreloxetine hydrochloride (0.3-60 mg/kg; PO; single dose) is irrespective between plasma concentration and dose level in rat model^[1].

Animal Model:	Rat^[1]
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 EC₅₀ for occupancy was 11.7ng/mL for NET and 50.8ng/mL for SERT in rat spinal cords, and the projected human plasma EC₅₀ values were 5.5ng/mL for NET and 23.9ng/mL for SERT.

IC 50

human Norepinephrine transporter: 8.0 (pIC₅₀); human Serotonin transporter: 8.6 (pIC₅₀); rat Norepinephrine transporter: 7.9 (pIC₅₀); rat Serotonin transporter: 8.9 (pIC₅₀)

References

[1] Smith JA, et al. Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Int J Neuropsychopharmacol. 2014 Dec 13;18(2):pyu027. DOI:10.1093/ijnp/pyu027