The unfinished journey with modafinil and discovery of a novel population of modafinil-immunoreactive neurons

Sleep Medicine
Jian-Sheng LinM Jouvet

Abstract

Modafinil, a wake-promoting compound now used worldwide in sleep medicine, was initially regarded as a sedative compound because mice were so quiet with respect to locomotion after receiving it that this behavioral state was qualified as sedation. In the early 1980's when modafinil was first assessed by polysomnography in a cat in our laboratory, surprisingly, the cat spent the whole night awake without even one minute of sleep! This initial observation resulted subsequently in a series of basic and clinical studies in order to define the pharmacological profile of modafinil and its mode of action and, notably, to identify the brain targets by which modafinil acts to promote wakefulness. These studies were undertaken using pharmacologic approach coupled with the Cerveau isolé (brain transection) preparation, c-fos labelling and knockout mouse models. It was also in this context that we have developed a purified polyclonal antibody against modafinil. We expected that using immunohistochemistry with this antibody would allow us to localize the brain distribution of modafinil dosing. Surprisingly, we found discrete modafinil immunoreactive neuronal populations in several brain areas of modafinil-naive cats, rodents and humans. The...Continue Reading

Citations

Jan 18, 2020·Substance Abuse : Official Publication of the Association for Medical Education and Research in Substance Abuse·Ana Sousa, Ricardo Jorge Dinis-Oliveira
May 15, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Giulia FisconPaola Paci
Jun 5, 2021·CNS Neuroscience & Therapeutics·Damien DupontMartine Wallon
Jun 10, 2021·Journal of Medicinal Chemistry·Stefanie HagenowHolger Stark
Aug 17, 2021·British Journal of Pharmacology·Yan-Fei YangZhi-Li Huang

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