Orexin Neuropeptides (Hypocretins)

Orexin neuropeptides, also known as hypocretins, are chemicals produced by nerve cells in the hypothalamus, a region of the brain that plays a role in regulating sleep, wakefulness, and hunger. There are two types of orexin neuropeptides, orexin-A and orexin-B, that stimulate the release of other neurotransmitters and hormones, such as dopamine and norepinephrine, to promote wakefulness and alertness.

Deficiencies in orexin signaling have been implicated in several sleep disorders, including narcolepsy, a condition characterized by excessive sleepiness and sudden bouts of sleep. In individuals with narcolepsy, there is a loss of orexin-producing cells in the hypothalamus, leading to decreased orexin signaling and excessive sleepiness.

Drugs that increase orexin signaling, such as modafinil and armodafinil, are used to treat excessive sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea. These drugs work by enhancing the release of orexin and other wakefulness-promoting neurotransmitters in the brain.

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