discontinued · 1 listed
newest 2005spec sheet6 rows
Abbott Laboratories built ABT-239 as a drug-like, orally active histamine H3 antagonist with real human-development ambitions behind it, unlike most H3 tool compounds; it was investigated as a candidate for ADHD, Alzheimer's disease, and schizophrenia-related cognitive deficits. It bound the human H3 receptor with subnanomolar potency and more than 1000-fold selectivity over the other histamine receptor subtypes, and it worked in rodent cognition and stress models. Abbott dropped it from human trials after it showed QT interval prolongation, a cardiac liability serious enough to end clinical plans outright, and ABT-239 has since lived on purely as a widely used preclinical benchmark for newer H3 antagonists.
- improved cognitive performance in rodent stress and impairment models
- high selectivity for H3 over other histamine receptor subtypes
- drug-like oral bioavailability that got it further than most H3 tool compounds
- remains a standard positive-control compound in H3 antagonist research
- QT interval prolongation, the reason it was pulled from human development
- ABT-239 was more than 1000-fold selective for H3 over the other three histamine receptor subtypes, an unusually clean selectivity profile for its era; the QT signal that ended it came from an entirely separate off-target cardiac liability.
Mechanism
Potent, selective H3 receptor inverse / (human pKi ~9.4, rat pKi ~8.9), over 1000-fold selective versus H1, H2, and H4 receptors; increases histaminergic, cholinergic, and monoaminergic signaling by blocking presynaptic H3 autoreceptors.
Safetyrisks and cautions, not medical advice
Every account of the cardiac problem traces back to a single 2006 review by an Abbott pharmacologist rather than to a published trial, and no clinical study of ABT-239 appears in any trial registry, so the QT prolongation that ended its development has never been shown in a paper anyone can read. The practical consequence is the same either way: no human dose was ever established, no volunteer tolerability data exists, and the one liability on the record is a cardiac one. It is sold as a laboratory reagent and should be treated as one.
History
Developed by Abbott Laboratories in the early 2000s as a clinical candidate for ADHD, Alzheimer's disease, and cognitive impairment in schizophrenia; discontinued from human development after showing QT prolongation in cardiac safety testing, and repurposed since then as a standard preclinical research tool.
Subjective profileweighing the evidence above
A pharmacologically clean H3 antagonist undone by a cardiac side effect, not a lack of central activity.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Why was ABT-239 stopped?
It showed QT interval prolongation in cardiac safety testing, a risk factor for dangerous heart arrhythmias, which ended Abbott's human development plans.
Is ABT-239 still used in research?
Yes, it remains a widely used reference compound in animal studies of H3 antagonist pharmacology and cognition, despite never becoming a human drug.
Limitations of the evidence
- no chronic human tolerability data since clinical testing stopped early
- cardiac risk profile likely rules out any future human use
Adverse effects
- QT interval prolongation, the reason it was pulled from human development