RESEARCH MONOGRAPH · KDC-MN-054

CX-516 (Ampalex)

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

54/100

First-generation ampakine with short half-life, mostly superseded but historically important

CX-516 (Ampalex) is the molecule that essentially launched the ampakine field. Lynch and Rogers developed it at Cortex Pharmaceuticals in the early 90s as a positive allosteric modulator at AMPA receptors, and it ran through some of the first human trials of any AMPA-PAM. The Lynch and Granger work on synaptic LTP enhancement built the conceptual case, and the Cortex trials in schizophrenia cognitive symptoms and Alzheimer's disease followed.

The pharmacology is exactly what you'd expect from a first-generation ampakine. AMPA receptor positive modulation by slowing deactivation kinetics, broad behavioral signal across cognitive paradigms in rodents, and a clear LTP-enhancement profile in hippocampal slice preparations. The mechanism story is clean compared to most racetams.

The clinical story was less clean. The schizophrenia trials (Goff and colleagues) showed modest signal on some cognitive measures but didnt produce a knockout efficacy result. The Alzheimer's work was similarly inconclusive. Part of the issue was the pharmacokinetics, CX-516 has a short half-life (around 1.5 hours) that makes maintaining therapeutic exposure annoying, and the dosing schedules used in trials may not have produced sustained AMPA potentiation in the way the mechanism would require.

What we like: historically important as the first ampakine to reach humans, clean receptor pharmacology, well-characterized in slice and in vivo, and the SAR work that came out of optimizing it informed every later compound in the class.

What we dont like: the short half-life is a real research limitation, the cognitive efficacy signal in humans was inconsistent, and the molecule has been superseded by CX-546 and CX-614 for most modern research purposes. The benzoylpyrrolidine scaffold is also moisture-sensitive in ways that complicate storage.

Sourcing is reasonable but limited. A handful of research suppliers carry it, characterization varies, and the molecule has enough commercial history that reference standards are available if you push for them. HPLC validation is established.

For research, CX-516 is mostly of historical interest at this point. If you specifically want a benzoylpyrrolidine-class ampakine, this is the canonical example. For modern ampakine pharmacology work, the later CX-series compounds or PEPA tend to be more useful.

Evidence: 50
Mechanism: 70
Reliability: 55
Safety: 65
Sourcing: 50
Value: 50
Signal: 50
Staying power: 45

Plain-language summary Intrigue 48 / 100

CX-516 (ampalex) is the first benzoylpyrrolidine ampakine, developed at Cortex Pharmaceuticals. Phase 2 trials in schizophrenia and Alzheimer were inconclusive. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Benzoylpyrrolidine ampakine

The first ampakine to enter human clinical trials, developed at Cortex Pharmaceuticals as a mechanism prototype with limited efficacy.

Abstract

CX-516 (Ampalex; 1-(quinoxalin-6-ylcarbonyl)piperidine; CAS 154235-83-3; molecular formula C14H15N3O; molecular weight 241.29) was the first ampakine compound to enter human clinical trials, developed at Cortex Pharmaceuticals (now RespireRx Pharmaceuticals) under license from Gary Lynch and Gary Rogers at the University of California, Irvine. The compound is a benzoylpyrrolidine class AMPA receptor positive allosteric modulator. CX-516 advanced through Phase 2 trials in mild cognitive impairment, schizophrenia (cognitive symptoms), and fragile X syndrome, with mixed results that did not support advancement to Phase 3. The compound has poor pharmacokinetic properties (very short plasma half-life, approximately 1 to 2 hours, and low oral bioavailability) which limit its clinical utility despite mechanistic interest. CX-516 retains research utility as an AMPA potentiator probe but is largely superseded by later-generation compounds (CX-546, CX-614, and others). Reported research dose ranges in the trial literature span 200 to 1200 mg. The compound is sold as a research chemical in jurisdictions where it is not scheduled.

Mechanism of action

AMPA receptor positive allosteric modulator (benzoylpyrrolidine class). First-in-class clinical compound.

Reported research dose ranges

Reported research dose ranges in the trial literature span 200 to 1200 mg.

References

Arai AC, et al. A centrally active drug that modulates AMPA receptor gated currents. Brain Res 1996.
Berry-Kravis E, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. Cogn Behav Neurol 2008.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, reported research dose ranges, sourcing and quality verification, reconstitution and handling, stack interaction considerations, and a curated reference list. Available as a research-use-only PDF download.

KDC-MN-054

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

Kodiac sells research compounds for investigative use only.

CX-516 (Ampalex)

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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