| Autor: |
Jian-Sheng Lin, Yves Dauvilliers, Isabelle Arnulf, Hélène Bastuji, Christelle Anaclet, Régis Parmentier, Laurence Kocher, Masashi Yanagisawa, Philippe Lehert, Xavier Ligneau, David Perrin, Philippe Robert, Michel Roux, Jeanne-Marie Lecomte, Jean-Charles Schwartz |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
|
| Zdroj: |
Neurobiology of Disease, Vol 30, Iss 1, Pp 74-83 (2008) |
| Druh dokumentu: |
article |
| ISSN: |
1095-953X |
| DOI: |
10.1016/j.nbd.2007.12.003 |
| Popis: |
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 H3-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. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for 1 week, the Epworth Sleepiness Scale (ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo (p>0.05) and 5.9 with tiprolisant (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full Text from ScienceDirect