Treatment with Samelisant (10 and 30 mg/kg, p.o.) produces a significant increase in wakefulness with a concomitant decrease in non-rapid eye movement sleep (NREM) sleep in orexin knockout mice subjected to sleep electroencephalography (EEG). Samelisant also produces a significant decrease in direct rapid eye movement (REM) sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy. Samelisant treatment in mice produces a dose-dependent increase in tele-methylhistamine levels indicating the activation of histaminergic neurotransmission.