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LY392098 was an early entry in Eli Lilly's biarylpropylsulfonamide AMPA potentiator series, and it did double duty in the company's research: as a tool for studying prefrontal cortical electrophysiology, and as one of the first pieces of evidence that boosting AMPA signaling could act like an antidepressant. In 2001 Lilly researchers published a trio of papers showing it potentiated AMPA currents selectively, without touching NMDA or kainate receptors, and reduced immobility in the forced swim test at a minimum effective dose of 0.5 mg/kg without moving serotonin or norepinephrine levels; a genuinely different antidepressant mechanism years before ketamine made glutamate a household word in psychiatry. Less potent than its stablemate LY404187, LY392098 stayed a research compound and was never taken into human trials as far as the public record shows.
- Reduced immobility in forced swim test antidepressant models
- Selective AMPA potentiation with minimal NMDA/kainate cross-activity
- Enhanced electrophysiological responses in prefrontal cortical neurons
- Established early proof-of-concept for glutamatergic antidepressants
- Lower potency than sibling compound LY404187, likely a factor in it being deprioritized
- LY392098 reduced immobility in the forced swim test at a minimum effective dose of just 0.5 mg/kg in rodents.
- It has essentially no activity on NMDA receptors, kainate receptors, or voltage-gated calcium channels, making it a very clean AMPA-selective pharmacology tool.
Mechanism
Binds an extracellular site on native receptors, potentiating responses with minimal off-target activity at , kainate (GluK5), or voltage-gated calcium channels.
Safetyrisks and cautions, not medical advice
Nothing is known about how this behaves in a person. LY392098 was characterised in three companion papers on rat receptors, rat cortical neurons and rodent behaviour, and no human trial of it appears anywhere in the public record, which leaves the dose, the tolerability and the interaction profile all blank. Its siblings in the same Lilly series carry a class concern about overexcitation at high exposure, since potentiating AMPA receptors is by design a way of making neurons fire more readily.
History
Published in a set of three companion papers in Neuropharmacology in 2001 covering in vitro receptor pharmacology, prefrontal cortical electrophysiology, and antidepressant-like behavior; no evidence of clinical development beyond this preclinical work.
Subjective profileweighing the evidence above
One of the earliest hard demonstrations that an AMPA potentiator could behave like an antidepressant in animals, and a mechanism nobody bothered chasing into humans until ketamine forced the issue years later.
Resources
This entry is here for reference.
Research
- 1.Pharmacological effects of AMPA receptor potentiators LY392098 and LY404187 on rat neuronal AMPA receptors in vitro
- 2.LY392098, a novel AMPA receptor potentiator: electrophysiological studies in prefrontal cortical neurons
- 3.Antidepressant-like actions of an AMPA receptor potentiator (LY392098)
3 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Did LY392098 ever get tested as an antidepressant in people?
No published record shows it advancing to human trials. Its antidepressant-like effects were demonstrated only in rodent behavioral despair models.
How does LY392098 relate to today's interest in glutamate antidepressants?
It was one of the first compounds to show that potentiating AMPA receptors, rather than blocking NMDA receptors like ketamine does, could produce antidepressant-like effects in animals, an idea that predated the ketamine-for-depression era by more than a decade.
Limitations of the evidence
- No published human safety or efficacy data
Adverse effects
- Lower potency than sibling compound LY404187, likely a factor in it being deprioritized