Orexin B
Hypocretin-2 neuropeptide (OX2-preferring) — investigational; ≠ orexin A ≠ DORA hypnotics.
Editorial review:Evidence snapshot
This drawer marks papers. It is not a plan, a dose, or a source. A paper is a bounded report. It is not a protocol. Grades name the object. They are not a safety rating.
Identity lock. Orexin B (also hypocretin-2) is a 28-amino-acid hypothalamic neuropeptide, co-discovered with orexin A / hypocretin-1. PubChem CID 44404987; formula C123H212N44O35S / MW 2899.3; CAS 205599-76-4. It preferentially engages the OX2 / HCRTR2 receptor relative to orexin A’s broader OX1/OX2 profile. Orexin B ≠ orexin A; ≠ dual orexin receptor antagonists (DORAs) used as labeled hypnotics; ≠ gray-market “orexin” vials as approved sleep drugs. This drawer marks papers. It is not use advice.
Bottom line
Foundational 1998 discovery papers define the orexin/hypocretin system and feeding/sleep biology. Later work includes OX2-preferring orexin-B analogues, midbrain glutamate transmission, cardiac OX2 myocardial-protection models, and receptor-pharmacology / sleep-phase reviews. Human clinical efficacy for exogenous orexin-B peptide as a therapeutic is not established in this set; labeled DORA hypnotics are a different object class.
Papers
Discovery / system definition
PMID 9491897 — Sakurai 1998
Tested: identification of orexins (orexin-A and orexin-B) and orexin receptors as hypothalamic neuropeptides regulating feeding behavior.
Does not show: a human therapeutic trial of exogenous orexin-B peptide, or interchangeability with orexin-A.
PMID 27909990 — Kukkonen 2017
Tested: review of orexin/hypocretin signaling biology.
Does not show: clinical approval of orexin-B peptide administration for sleep or metabolic indications.
PMID 34052813 — Sun 2021
Tested: hypocretin/orexin receptor pharmacology and sleep-phase framing.
Does not show: that exogenous orexin-B peptide equals a labeled insomnia or narcolepsy drug; DORA antagonists are opposite-direction pharmacology.
OX2-preferring analogues / physiology
PMID 12467628 — Asahi 2003
Tested: development of an orexin-2 receptor selective agonist analogue, [Ala11, D-Leu15]orexin-B.
Does not show: a completed human Phase 3 package for the parent orexin-B peptide.
PMID 18793323 — Borgland 2008
Tested: orexin B / hypocretin-2 increases glutamatergic transmission to ventral tegmental area neurons (rodent electrophysiology).
Does not show: human behavioral or therapeutic efficacy.
PMID 11790816 — Grudt 2002
Tested: hypocretin-2 (orexin-B) modulation of superficial dorsal horn activity in rat.
Does not show: human analgesia indication.
Cardiac OX2 context (preclinical)
PMID 30467191 — Patel 2018
Tested: functional cardiac orexin receptors; role of orexin-B / OX2 in myocardial protection models.
Does not show: a labeled cardioprotective orexin-B product in humans.
PMID 30948623 — Imperatore 2019
Tested: role of orexin-B / OX2 in myocardial protection (related cardiac framing).
Does not show: human cardiac outcome trials of orexin-B peptide.
Assay / localization context
PMID 10808249 — Mitsuma 2000
Tested: radioimmunoassay for hypocretin-2.
Does not show: therapeutic use; measurement method paper.
PMID 29496265 — Liguori 2018
Tested: localization of orexin B and OX2 in rat epididymis.
Does not show: human reproductive indication.
What is not established
Human clinical efficacy of exogenous orexin-B peptide for sleep, appetite, cognition, or cardioprotection. Equivalence to orexin A. Equivalence to dual orexin receptor antagonist hypnotics (opposite pharmacology). Product identity of unlabeled “orexin B” preparations versus research standards. This drawer does not provide use advice, schedules, or sourcing.
Selected sources
9491897 27909990 34052813 12467628 18793323 11790816 30467191 30948623 10808249 29496265
Reported experiences
Reported topics are not established benefits.Risks and unknowns
Compare experiences with care.
Join the discussion
Verified members can contribute to compound conversations.