spec sheet11 rows
CX-516 (Ampalex) is the first-in-class ampakine, developed by Cortex Pharmaceuticals, historically important as the compound that established AMPA-receptor positive modulation as a cognition strategy. It facilitates long-term potentiation and memory in animal models, but its weak potency and short half-life undermined every human trial.
- First-in-class ampakine that established AMPA-receptor potentiation as a cognition strategy
- Facilitates long-term potentiation and memory in animal models
- Increases BDNF expression preclinically
- Fatigue
- Insomnia
- Epigastric discomfort
- Allergic rash (~12.5% in the fragile-X trial)
- CX-516 was the first-in-class ampakine, the compound that put AMPA-receptor modulation on the cognition map.
- Its short half-life and weak potency are blamed for its negative human trials.
- It was tested as an add-on to the antipsychotic clozapine in schizophrenia.
Mechanism
-receptor positive modulator with low potency. It enhances excitatory transmission, facilitates , and increases expression in preclinical models.
receptor fingerprint
receptorsPositive allosteric modulation (low potency)
Hippocampal Facilitation
Upregulation (downstream)
Evidencehow good the literature is
Positive preclinical data but three essentially negative human RCTs. A small clozapine add-on pilot in schizophrenia (n~19) showed moderate-to-large effect sizes on attention and memory (Goff 2001), but the larger definitive schizophrenia trial (n=105) found no cognitive benefit (Goff 2007), and a fragile-X trial (n=49) was negative (Berry-Kravis 2006). The compound's weak potency and short half-life are widely blamed. Preclinically it facilitates LTP and reverses PCP-induced novel-object-recognition deficits.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Generally well tolerated in trials. Reported adverse events include fatigue, insomnia, and epigastric discomfort; about 12.5% of participants in the fragile-X study had an allergic rash. It is understudied for chronic use.
History
Developed by Cortex Pharmaceuticals as the first-in-class ampakine, also known as Ampalex and BDP-12. It was evaluated in three human RCTs: a clozapine add-on pilot in schizophrenia (Goff 2001), a definitive schizophrenia trial (Goff 2007, n=105), and a fragile-X syndrome trial (Berry-Kravis 2006). Cognitive results were essentially negative, attributed to weak potency and short half-life.
Reputation
Revered in nootropic history as the prototype ampakine that put AMPA-receptor modulation on the cognition map, but widely acknowledged as a clinical proof-of-concept that failed. Grey-market use is anecdotal and unstandardized.
Subjective profileweighing the evidence above
Foundational and heavily human-tested, but essentially negative for cognition at achievable doses. CX-516 is best understood as a landmark proof-of-concept that did not pan out clinically. Any grey-market nootropic use rests on no positive human efficacy data and is not supported here as a proven cognitive enhancer.
Resources
This entry is here for reference.
Research
- 2001first citedA placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia.
- 2010most recentPositive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor…
- 1.A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia.
- 2.A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia.
- 3.Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial.
- 4.Glutamate-based therapeutic approaches: ampakines.
- 5.Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats.
5 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Does CX-516 improve cognition in humans?
Not at achievable doses. Three human RCTs were essentially negative: a small clozapine add-on pilot showed signals, but the definitive schizophrenia trial (n=105) and a fragile-X trial (n=49) found no benefit. Weak potency and short half-life are blamed.
Why is it historically important?
It was the first-in-class ampakine (Cortex Pharmaceuticals) and established AMPA-receptor positive modulation as a cognition-enhancement strategy, a proof-of-concept that ultimately did not pan out in the clinic.
Is it sold as a nootropic?
Only grey-market and unstandardized, resting on no positive human efficacy data.
Adverse effects
- Fatigue
- Insomnia
- Epigastric discomfort
- Allergic rash (~12.5% in the fragile-X trial)