Firazorexton

Firazorexton (TAK-994 free base) is an orally active, brain-permeable orexin type 2 receptor (OX2R) agonist. Firazorexton has the potential to improve narcolepsy like symptoms.

Firazorexton activates recombinant human OX2R (EC50 value was 19 nM)^[1].

Firazorexton (1, 3, 10, 30 mg/kg, oral) exerts a wakeful effect in mice by activating OX2R^[1].
Firazorexton (10 mg/kg oral) significantly increases wakefulness time in monkeys, but does not increase OX-A levels in pooled cerebrospinal fluid (CSF)^[2].

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.
[2]. Yamada R, et al. The orexin receptor 2 (OX2R)-selective agonist TAK-994 increases wakefulness without affecting cerebrospinal fluid orexin levels in cynomolgus monkeys. Pharmacol Biochem Behav. 2024 Jan;234:173690.