What is the Origin of Orexin System Suppression?

The orexin system was discovered in the late 1990s, and its critical role in narcolepsy and wakefulness quickly established it as a major target for sleep-disorder therapeutics. The term "suppression" is a direct reference to the mechanism of action of dual orexin receptor antagonists (DORAs), a class of hypnotics.

What is the Mechanism of Orexin System Suppression?

The orexin peptides, Orexin A and Orexin B, bind to their cognate receptors (OX1R and OX2R) on various nuclei throughout the brainstem and forebrain, stimulating excitatory neurotransmission and stabilizing the awake state. Suppression operates by blocking these receptors, thereby preventing the orexin signal from activating downstream wake-promoting monoaminergic and cholinergic neurons. This pharmacological intervention allows the endogenous sleep-promoting drive to prevail, facilitating sleep onset and continuity.

Orexin System Suppression ∞ Area

Orexin System Suppression

Meaning

Orexin System Suppression is the targeted pharmacological or physiological reduction of activity in the orexinergic (also known as hypocretinergic) system, a neuropeptide network originating in the hypothalamus that is crucial for promoting wakefulness and regulating appetite. Clinically, suppression is employed to facilitate the transition into and maintenance of sleep by dampening the potent wake-promoting signal. This intervention highlights the critical neuroendocrine control of the sleep-wake cycle.