Suvorexant, branded as Belsomra, is an insomnia medication that works by blocking orexin receptors in the brain. Orexin is a neuropeptide that promotes wakefulness, so blocking its receptors promotes sleep. Suvorexant is thought to exert its therapeutic effects for insomnia by inhibiting the wakefulness-promoting effects of orexin. A current study is investigating whether long-term use of suvorexant can slow the accumulation of amyloid plaques and tau tangles in the brain, which are hallmarks of Alzheimer's disease. The results so far suggest suvorexant may be able to temporarily reduce levels of these proteins.

1. SUVOREXANT
 Brand name : Belsomra
 is an orexin antagonist
 medication which is used in the
treatment of insomnia
 Chemical Name: [(7R)-4-(5-chloro-1,3-
benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-
yl][5-methyl-2-(2H-1,2,3-triazol-2-
yl)phenyl]methanone
 Suvorexant is taken by mouth.

2. Mechanism of action of survexant
 Orexin is a neuropeptide produced by the
hypothalamus. It promotes wakefulness, and
blocking its receptor promotes sleep.
 Suvorexant is thought to exert its therapeutic
effects in the treatment of insomnia by blocking the
orexin receptors and thereby inhibiting the effects
of the endogenous wakefulness-promoting orexin
neuropeptides orexin-A and orexin-B.
 The orexin neuropeptides are produced exclusively
by a relatively small population of 20,000 to 80,000
neurons located in the lateral hypothalamus in the
brain.

3. • Alzheimer’s disease begins when plaques of the protein amyloid beta
start building up in the brain. After years of amyloid accumulation, a
second brain protein, tau, begins to form tangles that are toxic to
neurons. People with Alzheimer’s disease start experiencing cognitive
symptoms such as memory loss around the time tau tangles become
detectable.

4. • In May 2022, a Phase 2 study began at Washington University to
assess the effect of two years of suvorexant on the accumulation of
brain amyloid. The study plans to enroll 200 cognitively normal
participants with PET evidence of amyloid accumulation and poor
sleep, who will take 20 mg suvorexant or placebo nightly. The primary
outcome will be change in brain amyloid by PET scan. Secondary
outcomes include tau PET, cognitive measures, and changes in plasma
and CSF markers of Aβ and tau, as well as blood and CSF
transcriptomic, proteomic, and lipidomic analysis, and microbiome
evaluation. Completion is anticipated in May 2026.

5. • Lucey and co-authors noted. In mouse models, dual orexin receptor
antagonists have been shown to decrease soluble amyloid-beta
levelsopens in a new tab or window and amyloid plaques.
• By 24 hours after the first dose, hyperphosphorylated tau levels had risen
while amyloid levels remained low in the high-dose group compared to the
placebo group. A second dose of suvorexant, administered on the second
night, sent the levels of both proteins down again for people in the high-
dose group.
• "If we can lower amyloid every day, we think the accumulation of amyloid
plaques in the brain will decrease over time," Lucey said. "If you can reduce
tau phosphorylation, potentially there would be less tangle formation and
less neuronal death."

6. • The study suggests that sleep medications may be able to slow or
stop the progression of Alzheimer's disease, though much more
research is required to confirm the viability of such a strategy.
Suvorexant, the sleeping aid used in the study, already holds FDA
approval for treating insomnia.