PF-04958242
ampa pam · protects verbal learning and memory from ketamine-induced impairment class / ampa pamspec sheet6 rows
PF-04958242 was Pfizer's AMPA receptor potentiator, and unusually for this drug class it actually cleared a real human test: in a 2017 study, healthy volunteers were given ketamine to induce NMDA-hypofunction cognitive deficits (a validated schizophrenia-like model), and PF-04958242 measurably protected their verbal learning, recall, and working memory performance against the ketamine hit. That's about as close as any ampakine has come to proving the concept works in people. Pfizer nonetheless terminated its own Phase 2 trial in 2016 during an internal portfolio prioritization, not because of a safety or efficacy failure. Biogen then acquired the asset in 2018, calling it a first-in-class, Phase 2b-ready compound, renamed it BIIB104, and pushed it into further cognitive-impairment-in-schizophrenia (CIAS) trials into the early 2020s. As of the mid-2020s it has not emerged as an approved product and appears to have stalled again.
- Attenuated ketamine-induced impairment in verbal learning and recall in healthy volunteers
- Improved working memory (2-back and spatial tasks) under NMDA-hypofunction challenge
- Well tolerated with no pharmacokinetic interaction with ketamine in Phase 1b testing
- Validated with a real human challenge-test model, rare for this drug class
- Did not reduce ketamine's psychotomimetic (psychosis-like) effects
- PF-04958242's international nonproprietary name (INN) is pesampator.
- Pfizer's own Phase 2 trial was terminated in 2016 for internal portfolio reasons, not because of a safety or efficacy problem, and Biogen still thought it was worth acquiring two years later.
Mechanism
potentiator that slows receptor desensitization, boosting signaling in cortical circuits implicated in the cognitive deficits of schizophrenia; effects were validated using the ketamine -hypofunction challenge model in humans.
Safetyrisks and cautions, not medical advice
What it failed to do is as informative as what it did. In the ketamine challenge study it protected memory without blunting ketamine's psychosis-like effects at all, so it is no shield against the psychotomimetic side of NMDA disruption. The later 195-patient trial ran twelve weeks with no deaths and only four serious adverse events across all three arms, most of them worsening schizophrenia rather than anything drug-specific. That trial also tracked ataxia on a dedicated scale, a nod to the class worry that pushing AMPA receptors too hard costs coordination and lowers seizure threshold; no such signal appeared at the doses tested.
History
Pfizer ran Phase 1b studies around 2013-2015, including the ketamine-challenge study published in Molecular Psychiatry in 2017; Pfizer terminated its internal Phase 2 program in September 2016 for portfolio reasons; Biogen acquired the asset in 2018, renamed it BIIB104, and ran a CIAS trial (NCT03745820) into the early 2020s with no public approval or further update since.
Subjective profileweighing the evidence above
The ampakine with the best human proof-of-concept data on record, passed between two major pharma companies, and it still hasn't made it out the other side.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Is PF-04958242 / BIIB104 an approved medication?
No. Despite promising Phase 1b human data, it has not been approved. Pfizer originally developed it, Biogen later acquired and renamed it BIIB104, and as of the mid-2020s it has not reached the market.
What is the ketamine challenge model and why does it matter here?
Researchers give healthy volunteers ketamine to temporarily produce NMDA-receptor-hypofunction cognitive deficits similar to those seen in schizophrenia, then test whether a drug can protect memory and cognition against that hit. PF-04958242 passed this test, which is unusually strong human evidence for an ampakine.
Limitations of the evidence
- Development paused twice across two different companies for non-safety reasons
Adverse effects
- Did not reduce ketamine's psychotomimetic (psychosis-like) effects
Notes and cautions
- No completed Phase 2 efficacy data has been published