Uses
ACT-462206 is a potent and selective dual orexin receptor antagonist (DORA) that inhibits the stimulating effects of the orexin peptides at both the orexin 1 and 2 receptors. It decreases wakefulness and increases non-rapid eye movement (non-REM) and REM sleep while maintaining natural sleep architectures in some animal models while showing anxiolytic-like properties without affecting cognition and motor function in others.
Biological Activity
ACT-462206 is a orally active, brain penetrant, potent and selective dual orexin1/2 receptor antagonist (DORA). ACT-462206 decreases wakefulness, decreases sleep latency, and increases sleep efficacy in rats and dogs.', 'ACT-462206 is a proline sulphonamide with the potential to tre at insomnia. On absorption, its displays asthenia, blurred vision, and fatigue as adverse events.
in vivo
ACT-462206 (compound 24) (100 mg/kg; p.o.; sampling at 3 h) can go cross blood brain barrier, with concentrations are 2267 ng/mL and 1219 ng/g in plasma and brain, respectively in male Wistar rats[1].
ACT-462206 (10-300 mg/kg; p.o.; single dose) shows sleep-promoting effects in male Wistar rats and in male Beagle dogs, with decreasing wakefulness and increasing non-rapid eye movement (non-REM) and REM sleep[1].
ACT-462206 (100, 300 mg/kg; p.o.; single dose) exerts anxiolytic-like effects, decreases the fear-potentiated startle reflexes in response to a sudden loud noise in rats, reduces the socialstress-induced increases of locomotion, body temperature, and heart rate[1].
Pharmacokinetics in different species[1]
| Route | Dose (mg/kg) | AUC (ng h/mL) | CL (mL/min/kg) | Vss (L/kg) | t1/2 (h) | cmax (ng/mL) | tmax (h) | F1/2 (%) |
| rat | i.v. | 1 | 586 | 29 | 1.8 | 1.9 | / | / | / |
| p.o. | 10 | 2310 | / | / | / | 1600 | 0.5 | 39 |
| dog | i.v. | 1 | 1490 | 11 | 1.4 | 1.7 | / | / | / |
| p.o. | 3 | 2750 | / | / | / | 426 | 0.5 | 52 |
| Animal Model: | Male Wistar rats[1] |
| Dosage: | 0, 10, 30, 100, 300 mg/kg |
| Administration: | Oral gavage; single dose |
| Result: | Decreased the latency to the first persistent episode of non-REM sleep (60 s) and the first persistent episode of REM sleep (30 s).
Dose-dependently decreased total wake time and behavioral home cage activity (one-way ANOVA; p <0.001), while increasing REM and non-REM sleep times.
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