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 (pIC
50); human Serotonin transporter: 8.6 (pIC
50); rat Norepinephrine transporter: 7.9 (pIC
50); rat Serotonin transporter: 8.9 (pIC
50)
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
