Firazorexton hydrate (TAK-994) is an orally active and brain-penetrant orexin type 2 receptor (OX2R) selective agonist. Firazorexton hydrate can promote wakefulness and has the potential to improve narcolepsy-like symptoms in mice[1].
in vivo
Firazorexton (hydrate) (oral administration; 30 mg/kg; single dose) can increase the total wakefulness time in C57BL/6J mice[1].
Firazorexton (hydrate) (oral administration; 3-10 mg/kg; single dose) can improve narcolepsy-like symptoms in mouse models of narcolepsy[1].
Animal Model:
Orexin/ataxin-3 mice model[1]
Dosage:
3 and 10 mg/kg
Administration:
Oral administration (p.o.); single dose
Result:
Significantly increased total wakefulness time.
Decreased total NREM sleep time and REM sleep time.
Significantly ameliorated fragmentation of wakefulness with fewer number of wakefulness episodes and longer mean duration of wakefulness episodes.
Significantly increased gamma power during wakefulness at dose of 10 mg/kg.
IC 50
OX2 Receptor
References
[1] Ishikawa T, et al. TAK-994, a Novel Orally Available Brain-Penetrant Orexin 2 Receptor-Selective Agonist, Suppresses Fragmentation of Wakefulness and Cataplexy-Like Episodes in Mouse Models of Narcolepsy. J Pharmacol Exp Ther. 2023 Jun;385(3):193-204. DOI:10.1124/jpet.122.001449
