orexinergic

Orexinergic refers to the orexin system, consisting of neurons that produce the neuropeptides orexin A and orexin B (also known as hypocretins) and their receptors, OX1R and OX2R. Orexin-producing neurons are primarily located in the lateral and posterior hypothalamus, with extensive projections throughout the brain, including the cortex, thalamus, brainstem, and limbic regions. The term can describe neurons, pathways, or signaling mechanisms that involve orexin peptides or their receptors.

Functionally, the orexinergic system promotes wakefulness and arousal and coordinates energy homeostasis. Orexin neurons provide excitatory input to other arousal centers such as histaminergic, noradrenergic, and cholinergic systems, helping stabilize wakefulness and regulate sleep-wake transitions. The system also influences feeding behavior, reward processing, stress responses, and autonomic regulation, integrating metabolic and environmental signals to modulate behavior and physiology.

Clinical relevance centers on narcolepsy type 1, which involves loss or severe deficiency of orexin-producing neurons, leading to excessive daytime sleepiness, fragmented sleep, and cataplexy. Pharmacologically, orexin receptors are targets for sleep medicine. Dual orexin receptor antagonists (suvorexant, lemborexant, and daridorexant) are approved for the treatment of insomnia, promoting sleep by inhibiting orexin signaling. In contrast, orexin receptor agonists are under investigation for conditions such as narcolepsy and hypersomnia, aiming to enhance wakefulness through receptor activation.

The term "orexinergic" is used to describe neurons, circuits, or signaling pathways that use orexin peptides or interact with orexin receptors. The orexin system remains a focus of research due to its broad involvement in arousal, metabolism, and motivated behaviors, as well as its potential as a therapeutic target in sleep and metabolic disorders.