| Identification | Back Directory | [Name]
Piperidine, 4-[2-[(2,4,6-trifluorophenoxy)methyl]phenyl]-, hydrochloride (1:1) | [CAS]
1227056-87-2 | [Synonyms]
Ampreloxetine hydrochloride | [Molecular Formula]
C18H18F3NO.ClH | [MOL File]
1227056-87-2.mol | [Molecular Weight]
357.8 |
| Hazard Information | Back Directory | [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 |
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