ABSTRACT
The European experience on modafinil includes chemical, pharmacological, and clinical studies. Among the later are, studies on sleep (1-2), hormones (3) and cognitive functions (4-5) in healthy volunteers; alcoholic organic brain syndrome (6-7); cognitive performance during sleep deprivation experiments (8-9) and sustained military operations (10-11); residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome (12-13); fatigue in multiple sclerosis (14-15), excessive daytime sleepiness in Parkinson’s disease (16-17) and above all studies directed more closely towards narcolepsy, which will be developed in this chapter. All these studies have been concentrated in 3 countries, France, Austria, and the United Kingdom, in connection with Lafon Ltd, a company based in Maisons-Alfort (France), purchased by the U.S. company Cephalon in 2000. In this chapter we will concentrate on five aspects: the discovery of modafinil and the first trials in animals and humans; the first open-label study and the first multicenter, randomized, placebo-controlled trial of Modafinil in the treatment of excessive daytime sleepiness in narcolepsy; the c-fos immunocytochemical study carried out in the cat to identify the potential target neurons of modafinil and compare them with those for amphetamine and methylphenidate; the effect of the functional polymorphism of the catechol-O-methyltransferase (COMT) gene in the response to modafinil and the world longest open-label study (up to 20 years) in narcoleptic subjects treated with modafinil.
