RO5263397 是一种有效的，选择性的和口服的 TAAR1 激动剂，对人TAAR1 和大鼠 TAAR1 的 EC50 分别为 17 和 35 nM。RO5263397调节清醒度和 EEG 频谱组成。
RO5263397 is a potent, selective, and orally available TAAR1 agonist, with EC50s of 17 and 35 nM for human TAAR1 and rat TAAR1, respectively. RO5263397 regulates wakefulness and EEG spectral composition. Antidepressant-like effect[1][2][3].
RO5263397 (0.1-1.0 mg/kg; p.o.; dosing at the mid-light phase (ZT6)) increased wake time at 0.3 and 1 mg/kg[2].RO5263397 (0.3 and 1.0 mg/kg; p.o.) decreases NREM time in WT mice. RO5263397 (0.3 and 1.0 mg/kg; p.o.; in OE mice) powerfully increases W time in OE mice for 5-6 h. NREM sleep is suppressed for 4-6 h and REM sleep is almost completely suppressed for 6 h after all doses of RO5263397[3].
[1]. Galley G, et al. Discovery and Characterization of 2-Aminooxazolines as Highly Potent, Selective, and Orally Active TAAR1 Agonists.ACS Med Chem Lett. 2015 Dec 30;7(2):192-7.
[2]. Schwartz MD, et al. Trace Amine-Associated Receptor 1 Regulates Wakefulness and EEG Spectral Composition.Neuropsychopharmacology. 2017 May;42(6):1305-1314.
[3]. Espinoza S, et al. Biochemical and Functional Characterization of the Trace Amine-Associated Receptor 1 (TAAR1) Agonist RO5263397.Front Pharmacol. 2018 Jun 21;9:645.
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