Belsomra

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Belsomra is a medication used to treat the inability to fall asleep or stay asleep (1). While most other insomnia drugs, like Ambien and Lunesta, are GABA agonists and work to slow down neuronal firings, Belsomra is the first drug to target orexin (2). Orexin, also known as hypocretin, is a neurotransmitter that binds to receptors in order to cause alertness and wakefulness. By targeting these neurotransmitters, it cuts off the signals causing one to be awake, and will result in sleep (1).

Function

Structural highlights

Relationship to Insomnia

Insomnia is a sleep disorder that is seen to be mostly caused by stress, and results in inefficient cooperation between the sleep and wake pathways of the arousal system. The branch of the arousal system that reaches the lateral hypothalamus, which contains the melanin-concentrated orexin neuropeptide signaling system, is one of the most significantly affected areas of the wakefulness network. This orexin system is a major promoter for wakefulness and is most active during efforts to sustain and maintain arousal, while showing little activity during sleep. Orexins show little activity during sleep because the systems to promote wakefulness are blocked by neurons of the ventrolateral preoptic nucleus and thus cannot fire. During sleep, these VLPO neurons are activated and form dense clusters containing GABA and galanin, which aid in their function as inhibitors for arousal. With insomnia, the structures regulating a patient’s arousal system are unusually active during sleep, and thus the system fails to deactivate. Belsomra is a drug that counteracts this by serving as a dual antagonist in its interactions with Orexin receptors 1 and 2, in the aim of deactivating the arousal system in order for patients to sleep with little orexin activity present. This could also exacerbate the symptoms of narcolepsy, as the already little orexin activity would be diminished at great risk to patients with the sleep disorder.

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