| Autor: |
Smith, Jacqueline AM, Patil, DL, Daniels, OT, Ding, Y-S, Gallezot, J-D, Henry, S, Kim, KHS, Kshirsagar, S, Martin, WJ, Obedencio, GP, Stangeland, E, Tsuruda, PR, Williams, W, Carson, RE, Patil, ST |
| Předmět: |
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| Zdroj: |
International Journal of Neuropsychopharmacology; Jan2015, Vol. 18 Issue 2, p1-1, 1p |
| Abstrakt: |
Background: Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. Methods: We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Results: TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo. Conclusions: These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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