Orexin-B

Where it comes from

Made in

The same lateral hypothalamic neurons as orexin-A, cut from the same precursor

Sent out by

With orexin-A

Acts on

• Histamine neurons of the tuberomammillary nucleus (OX2R)
• Other arousal and feeding circuits

What it does

• Keeps the brain awake through OX2R, the receptor whose loss causes narcolepsy in dogs ¹
• Shorter-lived than orexin-A in blood and spinal fluid
• Drives feeding and gut motility like orexin-A

In medicine

• Covered by the orexin medicines: the dual blockers suvorexant, lemborexant and daridorexant switch off both the receptors it uses ³
• It is not measured in practice. The narcolepsy test reads orexin-A in spinal fluid, because orexin-B breaks down too fast to give a dependable number ¹

Beyond the body’s own use

• The orexin-2 selective agonists for narcolepsy are modelled on its selectivity rather than on orexin-A’s; oveporexton, the first of them, was approved in the United States in 2026 ²
• Nothing containing orexin-B is approved or available outside the laboratory. What is genuinely unsettled is whether the two peptides do different work at all: one gene makes both, so no animal exists that keeps one and loses the other ¹