data + articles · 2 listed
newest 2006spec sheet11 rows
SB-399885 is a potent, selective and orally active serotonin 5-HT6 receptor antagonist developed at GlaxoSmithKline as a cognition-enhancer research compound. It has very high 5-HT6 affinity and more than 200-fold selectivity over other receptors, ion channels and enzymes, making it one of the cleaner pharmacological probes for the receptor. In rodent studies it reversed scopolamine- and dizocilpine-induced memory deficits, improved spatial learning in aged rats and raised cortical acetylcholine. It was never marketed but is a well-validated tool antagonist widely used to test the 5-HT6 cognition hypothesis.
- Very high 5-HT6 affinity with over 200-fold selectivity
- Orally active and brain-penetrant
- Reversed scopolamine- and dizocilpine-induced memory deficits
- Fully reversed age-related spatial-memory deficit in aged rats
- Directly increased prefrontal-cortex acetylcholine
- Excellent pharmacokinetic-pharmacodynamic correlation
- Reliable positive-control antagonist for the field
Overview
SB-399885 is a benzenesulfonamide 5-HT6 receptor antagonist characterized at GlaxoSmithKline, with reported human 5-HT6 pKi values above 9 and more than 200-fold selectivity over all other receptors, ion channels and enzymes tested, together with good brain penetration and oral activity [1]. It shows an excellent pharmacokinetic-pharmacodynamic correlation, occupying central 5-HT6 receptors after oral dosing and displaying a long duration of action [1].
In behavioural pharmacology SB-399885 has a robust pro-cognitive profile. Repeated oral administration reversed a scopolamine-induced deficit in a rat novel-object-recognition task and, in 22-month-old aged rats, fully reversed an age-dependent deficit in Morris water-maze spatial learning while improving recall; in vivo microdialysis showed that acute dosing significantly increased extracellular acetylcholine in the medial prefrontal cortex, providing a cholinergic mechanism for the cognitive effects [1]. In a separate autoshaping learning paradigm, oral SB-399885, like the related antagonist SB-357134, improved memory consolidation and reversed deficits produced by scopolamine or dizocilpine [2].
Because of this clean, selective and orally active profile, SB-399885 became a favoured reference antagonist for testing the hypothesis that 5-HT6 blockade enhances cognition, and it is frequently used as a positive control against which agonists such as WAY-181187 and multi-target compounds such as latrepirdine are compared [2]. It was not developed into a marketed drug and remains a research tool.
- SB-399885 fully reversed an age-related spatial-memory deficit in 22-month-old rats, one of the cleaner demonstrations that 5-HT6 blockade can rescue cognition in aging.
- Microdialysis showed it directly raises acetylcholine in the prefrontal cortex, tying its memory effects to cholinergic activation.
Mechanism
SB-399885 is a highly selective competitive at the 5-HT6 receptor. By blocking 5-HT6 receptors on cortical and hippocampal interneurons it relieves inhibitory tone and increases downstream and release; the demonstrated rise in prefrontal- acetylcholine after dosing is a direct correlate of its cognition-enhancing activity. Its high selectivity minimizes confounding off-target effects.
receptor fingerprint
5-HT6 receptorHighly selective competitive antagonism
Prefrontal Increases extracellular acetylcholine
Memory consolidation and recallReverses scopolamine and dizocilpine deficits; improves aged-rat spatial learning
Evidencehow good the literature is
Preclinical only; robust and reproducible animal cognition data
Dosingtypical ranges, not medical advice
interested in protocols and clinical dosages? make an account to see them! ^_^
Safetyrisks and cautions, not medical advice
As a preclinical research compound, SB-399885 has no established human safety profile. In rodents it was orally active and behaviourally effective without notable toxicity at studied doses, and it caused inappetence only at higher doses, but it is not intended for human use and lacks any clinical tolerability data.
History
SB-399885 was developed within GlaxoSmithKline's 5-HT6 programme in the mid-2000s as a next-generation, orally active, selective antagonist for cognitive disorders such as Alzheimer's disease and schizophrenia. It served principally as a preclinical reference and did not advance to a marketed therapeutic, but it remains one of the most cited tool antagonists in the field.
Reputation
SB-399885 is regarded by researchers as a gold-standard selective 5-HT6 antagonist for behavioural pharmacology, valued for its clean profile, oral activity and reproducible pro-cognitive effects. It has no status as a consumer nootropic and is understood as a research chemical.
Subjective profileweighing the evidence above
A research probe, not a nootropic. It is one of the cleanest 5-HT6 antagonists ever made and the rodent memory data is robust and reproducible, but it never went into humans, so there is no safety or efficacy record to lean on.
Resources
This entry is here for reference.
Research
- 1.SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models
- 2.Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What makes SB-399885 useful to researchers?
It is a highly selective, orally active 5-HT6 antagonist with reproducible pro-cognitive effects, making it a clean positive control for studying the receptor.
How does it improve memory in animals?
It blocks 5-HT6 receptors on inhibitory neurons, raising acetylcholine in the prefrontal cortex and enhancing memory consolidation and recall.
Is it a drug I can take?
No. It is a preclinical research chemical with no human safety data and is not a consumer nootropic.
How does it relate to SB-271046?
Both are selective GlaxoSmithKline-lineage 5-HT6 antagonists; SB-399885 is a later, orally active tool frequently used together with or instead of SB-271046.
Did it become a medicine?
No. It remained a research tool and was not developed into an approved therapeutic.
Limitations of the evidence
- No human safety or efficacy data
- Never developed into a marketed therapeutic
Notes and cautions
- Inappetence observed at higher doses in animals
- Strictly a research chemical, not for consumption