Possible Mechanism Of Action Of Provigil-Induced Wakefulness Identified

West Chester, PA - November 29, 2000

Cephalon, Inc. reports that a preclinical study published in the November 15 issue of the Journal of Neuroscience provides further evidence that PROVIGIL(R) (modafinil) activates specific neuronal pathways that are believed to regulate normal wakefulness. In this study, modafinil strongly activated two well- defined groups of nerve cells located in the hypothalamus that have been implicated in the control of wakefulness - the tuberomammillary nucleus (TMN) and orexin-containing nerve cells. This mechanism of action is different from the pathways affected by traditional stimulants.

In three separate studies, modafinil was administered to rats at different times of day in combination with physiological recordings of sleep/wake behavior. The degree of nerve cell activation was then measured in various areas of the brain. Results of these experiments showed that nerve cells in the TMN were four times more active in rats administered modafinil than in control animals. In addition, the number of activated orexin-containing nerve cells in the hypothalamus increased threefold in rats administered modafinil.

According to Dr. Thomas Scammell, M.D., Assistant Professor in the Department of Neurology at Beth Israel Deaconess Medical Center and lead author of the study, "This is an exciting finding because it represents the first demonstration of a drug directly activating these regions of the brain. Selective activation of these regions may represent a novel approach to producing wakefulness that is free of amphetamine-like subjective effects."

PROVIGIL(R) (modafinil) was approved by the Food and Drug Administration (FDA) in December 1998 as a once-a-day therapy to improve wakefulness in patients experiencing excessive daytime sleepiness associated with narcolepsy. The most frequently reported adverse events observed in clinical trials for narcolepsy were headache, nausea, nervousness, anxiety, infection and insomnia. The exact mechanism of action of PROVIGIL is not known.

Cephalon, Inc., headquartered in West Chester, Pennsylvania, is an international biopharmaceutical company dedicated to the discovery, development and marketing of products for sleep disorders, neurological disorders, pain management and cancer.