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CX-717 is a later, more brain-penetrant ampakine (Cortex Pharmaceuticals, later RespireRx) notable for offsetting sleep-deprivation cognitive decline in nonhuman primates and, at high dose, in humans, plus a distinct adult-ADHD development track. It has a 'low-impact' AMPA-PAM profile.
- Brain-penetrant, 'low-impact' AMPA-PAM profile
- Offset sleep-deprivation cognitive decline in primates and, at 1000 mg, in humans
- Positive trend and hyperactivity-subscale signal in adult-ADHD trials
- Increases regional brain glucose metabolism in prefrontal and hippocampal regions
- Sleep disturbance and headache (most common adverse events)
- In sleep-deprived humans, only the highest 1000 mg dose of CX-717 improved attention, and it reduced slow-wave recovery sleep.
- Its clinical development was repeatedly held back by animal toxicology showing brain histopathological changes.
- A 2025 crossover ADHD trial missed its primary endpoint but a secondary analysis favored the 800 mg twice-daily dose.
Mechanism
-receptor positive modulator with a 'low-impact' profile. It enhances transmission and increases regional cerebral glucose metabolism (CMRglc) in the prefrontal , striatum, and medial temporal lobe/.
receptor fingerprint
receptorsPositive allosteric modulation ('low-impact' profile)
Prefrontal transmissionEnhancement
Regional cerebral glucose metabolism (CMRglc)Increase in prefrontal cortex, striatum and hippocampus
Evidencehow good the literature is
Strong nonhuman-primate data plus a partial human signal. Boyle 2011 (n=16, sleep deprivation) found that only the 1000 mg dose improved attention-based tasks (and it reduced slow-wave sleep). A Cortex Phase 2a adult-ADHD study (~49 patients, 800 mg BID) reported a positive trend with a significant hyperactivity-subscale effect, and a 2025 RespireRx crossover (n=68) missed its primary endpoint (p=0.151) but a secondary analysis favored the 800 mg dose (p=0.002 on total ADHD-RS). Notably, the FDA declined Cortex's Phase IIb ADHD IND in 2007 over animal brain histopathology, and one rat study found impaired object recognition.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Well tolerated in human trials with no cardiovascular signals at ADHD doses; sleep disturbance and headache were the most common adverse events. The significant caveat is animal toxicology: histopathological brain changes drove FDA clinical holds, including the 2007 declined Phase IIb ADHD IND. One rat study also found CX-717 impaired object-recognition memory. These are genuine, honest red flags.
History
Developed by Cortex Pharmaceuticals (later RespireRx) as a more brain-penetrant ampakine. It offset sleep-deprivation deficits in nonhuman primates (Porrino 2005) and in humans at 1000 mg (Boyle 2012). Cortex's Phase 2a adult-ADHD trial (~49 patients, 800 mg BID) reported a positive trend, but the FDA declined the Phase IIb ADHD IND in 2007 over animal brain histopathology. A 2025 RespireRx crossover (n=68) missed its primary endpoint but a secondary analysis favored the 800 mg dose.
Reputation
Known in nootropic circles for its wakefulness and anti-sleep-deprivation angle, and cited as one of the few ampakines with real nonhuman-primate and human sleep-deprivation data. Its reputation is tempered by repeated animal-toxicology FDA holds and the fact that it remains understudied for general cognitive use.
Subjective profileweighing the evidence above
There is a modest but real human signal in specific contexts (sleep loss and ADHD), but clinical development was repeatedly hampered by an animal-toxicology FDA hold, and it is understudied for general nootropic use. It should be presented as an investigational compound with a partial, context-specific human signal and a genuine safety caveat, not as a proven cognitive enhancer.
Resources
This entry is here for reference.
Research
- 2005first citedFacilitation of task performance and removal of the effects of sleep deprivation by an ampakine…
- 2025most recentLow-impact ampakine CX717 exhibits promising therapeutic profile in adults with ADHD - A phase…
- 1.Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates.
- 2.Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep.
- 3.Effects of the putative cognitive-enhancing ampakine, CX717, on attention and object recognition memory.
- 4.Low-impact ampakine CX717 exhibits promising therapeutic profile in adults with ADHD - A phase 2A clinical trial.
4 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Does CX-717 work as a nootropic?
Only a modest, context-specific human signal exists. In sleep-deprived volunteers only the 1000 mg dose improved attention tasks, and an adult-ADHD program showed a positive trend at 800 mg twice daily. It is not a proven general cognitive enhancer.
What is the safety red flag?
Animal toxicology found histopathological brain changes, which drove FDA clinical holds; the Phase IIb ADHD IND was declined in 2007. Human trials were otherwise well tolerated, but this is a genuine caveat.
How is it different from earlier ampakines?
It is more brain-penetrant with a 'low-impact' profile, and it has real nonhuman-primate and human sleep-deprivation data plus a distinct ADHD development track.
Limitations of the evidence
- Animal toxicology showed brain histopathological changes (FDA clinical holds)
- Impaired object-recognition memory in one rat study
Adverse effects
- Sleep disturbance and headache (most common adverse events)
Notes and cautions
- Generally well tolerated in human trials