LY404187
ampa pam · potentiates ampa receptor currents with unusual time-dependent kinetics class / ampa pamspec sheet6 rows
LY404187 was one of the most potent compounds to come out of Eli Lilly's early-2000s AMPA receptor potentiator program, a biarylpropylsulfonamide engineered to suppress receptor desensitization with a distinctive, slowly-growing time course unlike anything seen with older potentiators like cyclothiazide or aniracetam. Researchers used it to prove, in a fairly dramatic way, that AMPA potentiation alone could switch on broad swaths of brain metabolic activity; a 2004 study showed it drove cerebral glucose utilization and c-fos expression widely across the rat brain. It was also tested alongside LY503430 for neurotrophic rescue in Parkinson's disease models. Despite the strong pharmacology, LY404187 stayed a Lilly screening and mechanism-validation tool rather than a clinical candidate, and there's no record of it ever reaching human testing.
- Among the most potent AMPA receptor potentiators characterized by Lilly
- Drove measurable increases in brain glucose metabolism in rodent studies
- Showed neurotrophic promise in Parkinson's disease models
- Useful reference compound for AMPA receptor pharmacology research
- A single dose of LY404187 was shown to increase cerebral glucose utilization broadly across the rat brain, a striking demonstration of how much metabolic activity AMPA potentiation alone can drive.
- In potency rankings from Lilly's own comparative studies, LY404187 beat out LY392098, cyclothiazide, CX-516, and aniracetam.
Mechanism
Preferentially potentiates recombinant human GluA2 and GluA4 homomeric receptors over GluA1/GluA3, suppressing receptor desensitization with a unique time-dependent growth in effect; also indirectly recruits voltage-dependent activity.
Safetyrisks and cautions, not medical advice
Use of LY404187 never went past the laboratory bench, so its risk profile in people is undefined; nobody has published a human dose for it, a tolerability report on it, or any human safety pharmacology. What the rodent work does show is the mechanism cutting both ways, because a single dose raised glucose utilisation and c-fos expression across wide areas of the rat brain, which is a picture of broad neuronal activation. Potentiating AMPA receptors hard enough to do that is the same property that gives this chemical family a seizure concern.
History
Characterized by Lilly researchers starting in 2001-2002, with follow-up studies in 2004 on cerebral glucose utilization and Parkinson's disease neurotrophic effects. No public record of clinical-phase testing exists.
Subjective profileweighing the evidence above
The most potent proof-of-concept in Lilly's ampakine toolkit, used to validate the whole AMPA-potentiator idea in the lab, but never turned into an actual drug candidate.
Resources
This entry is here for reference.
Research
- 1.LY404187: a novel positive allosteric modulator of AMPA receptors
- 2.The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat
- 3.Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson's disease
3 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Was LY404187 ever developed as a drug?
No. It was used extensively as a pharmacology tool to validate AMPA receptor potentiation as a mechanism, but there's no evidence it was ever taken into human clinical trials.
How does LY404187 compare to older AMPA potentiators like aniracetam?
In head-to-head potency rankings, LY404187 was more potent than LY392098, which in turn outranked cyclothiazide, CX-516, and aniracetam, making it one of the strongest AMPA potentiators characterized at the time.
Limitations of the evidence
- No human safety or tolerability data exists
- Never advanced past preclinical/pharmacology-tool status