The main purpose of these studies is to understand better how sleep disorders start and how they are progressing, and also what the reason is for this.

Provigil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which Provigil acts, we administered a range of doses of Provigil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry.
To contrast Provigil-induced wakefulness with spontaneous wakefulness, we administered Provigil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected Provigil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg Provigil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of Provigil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala.
It is now well accepted that transitions between sleep and wakefulness are regulated by complex neurobiologic mechanisms, which, ultimately, can be delineated as oscillations between two opponent processes, one promoting sleep and the other promoting wakefulness.
The role of several neurotransmitter or neuromodulator systems, including noradrenergic, serotonergic, cholinergic, adenosinergic, and histaminergic systems and, more recently, the hypocretin/orexin and dopamine systems, has been clearly established.
Amphetamine-like stimulants are known to increase wakefulness by blocking dopamine reuptake, by stimulating dopamine release, or by both mechanisms.
The NDA is based on positive results of four double-blind, randomized, placebo-controlled studies of NUVIGIL in patients with excessive sleepiness associated with either narcolepsy, SWSD or OSA/HS. The data in this filing show that the primary endpoints of all studies were met and suggest that NUVIGIL is differentiated from PROVIGIL.
“This is the third of five FDA approvals that we will be pursuing over a 15-month time period,” said Dr. Paul Blake, Executive Vice President, Worldwide Clinical Research & Regulatory Affairs at Cephalon. “Cephalon is a pioneer in developing compounds for improving wakefulness, and this on- schedule filing allows us to reinforce our leadership position in the treatment of disorders of sleep and wakefulness,” added Dr. Blake.