Journal article

An inverse agonist of the histamine H-3 receptor improves wakefulness in narcolepsy: Studies in orexin(-/-) mice and patients

Jian-Sheng Lin, Yves Dauvilliers, Isabelle Arnulf, Helene Bastuji, Chnistelle Anaclet, Regis Parmentier, Laurence Kocher, Masashi Yanagisawa, Philippe Lehert, Xavier Ligneau, David Perrin, Philippe Robert, Michel Roux, Jeanne-Marie Lecomte, Jean-Charles Schwartz

NEUROBIOLOGY OF DISEASE | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2008

Abstract

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H(3)-receptor agonist. In narcoleptic orexin(-/-) mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently-prescribed wake-promoting drug...

View full abstract