Neurology Central

Novel compound could lead to new therapy for narcolepsy

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New research, published recently in the Journal of Medicinal Chemistry, has highlighted the successful development of a compound that could be used in the treatment of the sleep disorder narcolepsy.

The compound, which has so far been tested in animal models, functions through mimicking the action of the wake-promoting neuropeptide, orexin, within the brain. The molecule was originally discovered and highlighted as playing a key role in maintaining wakefulness in 1998 by Masashi Yanagisawa (University of Tsukuba), one of the lead authors on the current paper, and deficiencies in orexin have been linked to narcolepsy.

Despite orexin being proven as an effective treatment in models, its inability to pass through the blood-brain barrier prevents its direct therapeutic use. Due to this, the study’s lead author Hiroshi Nagase (University of Tsukuba) and his team focused on developing an orexin receptor agonist as a potential therapeutic agent.

The University of Tsukuba team designed and synthesized over 2000 different compounds, eventually identifying YNT-185 as the first non-peptidic orexin receptor agonist. In the mice models utilized, YNT-185 strongly promoted wakefulness and currently unpublished data indicates that in narcoleptic mice YNT-185 was able to significantly reduce the symptoms.

The team believe that this is an important step in the development of an effective treatment for narcolepsy, targeting the fundamental disease mechanism. “Our achievement opens up a realistic avenue towards a novel medicine for narcoleptic patients,” commented Nagase.

Source: University of Tsukuba press release

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