Modafinil: its discovery, the early European and North American experience in the treatment of narcolepsy and idiopathic hypersomnia, and its subsequent use in other medical conditions

Sleep Med. 2018 Sep;49:69-72. doi: 10.1016/j.sleep.2018.05.027. Epub 2018 Jun 6.

Abstract

Adrafinil, a new molecule identified by a French drug company, L. Lafon Ltd, in 1974, was found to cause a significant dose-dependent increase in motor activity in mice, without exerting peripheral sympathomimetic effects. As early as 1977-78, Michel Jouvet prescribed adrafinil to narcoleptic patients, but without consistent results. Meanwhile the kinetics of adrafinil led to the identification of an active metabolite, modafinil. In 1983, Jouvet and Bastuji prescribed modafinil to narcoleptic and idiopathic hypersomnia patients and obtained a significant decrease of excessive daytime sleepiness and sleep attacks in a majority of patients. L. Lafon Ltd was initially not interested in developing this molecule for market however, thanks to Jouvet's insistance, it decided to start clinical trials in both healthy volunteers and narcoleptic patients as well as conduct animal studies. Results were excellent and led to the use of modafinil by the French army during the Gulf War in January-February 1991, as well as to the official registration of the drug in France in 1992. Subsequent multicenter controlled clinical trials in North America confirmed the findings in Europe. Modafinil was later used to treat sleepiness, somnolence and fatigue in a large number of medical conditions.

Keywords: Adrafinil; General medicine; Hypersomnia; Modafinil; Narcolepsy; Sleep apnea.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / therapeutic use
  • Animals
  • Central Nervous System Stimulants / history*
  • Central Nervous System Stimulants / therapeutic use*
  • Clinical Trials as Topic
  • Disorders of Excessive Somnolence / drug therapy*
  • Europe
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Hydroxamic Acids / therapeutic use
  • Mice
  • Military Personnel
  • Modafinil / history*
  • Modafinil / therapeutic use*
  • Narcolepsy / drug therapy*
  • North America
  • Wakefulness

Substances

  • Adrenergic alpha-Agonists
  • Central Nervous System Stimulants
  • Hydroxamic Acids
  • adrafinil
  • Modafinil