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SB-334867 the original selective orexin-1 receptor antagonist; a non-drug research tool used in thousands of preclinical studies of addiction, feeding, anxiety and reward; not a therapy, and with known chemical-stability quirks.
- first and most-used selective OX1 antagonist probe
- mapped OX1's role in addiction, feeding, reward, and anxiety
- foundation for later clinical OX1-selective drugs
- chemical instability in solution
- possible loss of selectivity / off-target effects at high concentrations
Overview
if you have read any orexin paper from the 2000s-2010s, you have seen SB-334867. it was the first widely available selective OX1 blocker and it basically built the field's understanding of OX1 in reward, drug-seeking, and appetite. it is a lab tool, not a medicine, and it has some stability/selectivity caveats you should know if you read the literature.
- SB-334867 was the first selective OX1 antagonist, and it appears in a huge share of orexin research papers as the standard OX1 probe.
- much of what we know about orexin's role in addiction and cue-induced drug seeking came from SB-334867 experiments.
- it has real chemical-stability issues in solution and can lose selectivity at high concentrations, so careful researchers flag its high-dose results.
Mechanism
SB-334867 is a selective -1 receptor and was the first such tool compound available, which is why it appears in an enormous fraction of orexin literature. by blocking OX1R it reduces orexin's effects on reward, motivation, drug- and food-seeking, and stress reactivity, generally without the strong sedation of OX2 or dual block (again reflecting OX2 = sleep, OX1 = reward/stress). it has been used to show OX1's role in cue-induced reinstatement of drug seeking (cocaine, alcohol, nicotine), binge eating, and anxiety across many rodent studies (see fagan 2022 for the depression/behavioral literature). important caveats for interpreting that literature: SB-334867 has limited aqueous stability and can be less cleanly selective at higher concentrations, so results at high doses should be read carefully.
receptor fingerprint
OX1R (-1 / HCRTR1)selective competitive antagonist
OX2R (-2 / HCRTR2)much weaker (spared at usual concentrations)
Safetyrisks and cautions, not medical advice
research tool only; no human data and no therapeutic use. relevant caveats are scientific rather than clinical: chemical instability in solution and potential off-target/insulin-related effects reported at higher concentrations, which complicate interpretation of some older studies. not a medicine and not for human use.
History
developed by smithkline beecham/glaxosmithkline as the first selective OX1 antagonist tool compound; it predates all the clinical orexin drugs and was instrumental in mapping OX1 biology in addiction, feeding, and anxiety through the 2000s and 2010s. its ubiquity as a probe is a big reason OX1's role in reward and stress is as well characterized as it is, and it set the stage for clinical selective OX1 antagonists like nivasorexant.
Reputation
the workhorse OX1 tool compound; hugely important historically and still widely used, but researchers treat its high-dose results cautiously because of stability and selectivity limits. it has no clinical role.
Subjective profileweighing the evidence above
A lab reagent, and a slightly awkward one, since it degrades in solution and loses selectivity at high concentrations. Its legacy is the orexin research it made possible and the clinical OX1 drugs that followed, not any use of its own.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
is SB-334867 a medicine?
no; it is a laboratory research tool, the classic selective OX1 antagonist probe, with no human use or approval. it is used to study what OX1 receptors do.
why is SB-334867 in so many papers?
it was the first selective OX1 antagonist made widely available, so for years it was the only practical way to isolate OX1 effects. it became the default probe in orexin research on addiction, feeding, and anxiety.
are SB-334867 results reliable?
mostly, but with caveats. it has limited stability in solution and can become less selective at high concentrations, so careful researchers are skeptical of high-dose findings and confirm with newer, cleaner tools.
what did we learn from it?
a lot of the OX1 = reward and stress story: OX1 blockade reduces cue-induced drug and food seeking and dampens anxiety in animal models, without the sedation you get from blocking OX2.
Limitations of the evidence
- no human data; not a medicine
Adverse effects
- chemical instability in solution
- possible loss of selectivity / off-target effects at high concentrations