• Synthetic class of AMPA-receptor modulators
  • May improve memory
  • Could have anti-depressant effects
  • Possible neuroprotective
  • May be useful for treating schizophrenia
About Ampakines
Other names: CX compounds
Good for:
Pairs Well With:
Typical Dose: NA
Half Life: NA

Written by Erik Levi, FNTP — Updated on October 15, 2020

Ampakines – An Overview

ampakines nootropics
Ampakines modulate the activity of glutamate receptors.

Ampakines are a class of nootropic drugs that modulate the brain’s AMPA receptors and may have a positive effect on:1Zheng Y, et al. Effects of the putative cognitive-enhancing ampakine, CX717, on attention and object recognition memory, Curr Alzheimer Res. 2011

Ampakines may prove to be a novel new treatment for various conditions such as Alzheimer’s, Parkinson’s, treatment-resistant depression, ADHD, schizophrenia, and others.

The Strongest Nootropics?

One of the most interesting things about ampakines is their potency. These nootropics are up to 1000x more powerful than piracetam, the original nootropic supplement.

Despite their strength, ampakines do not seem to have the same side-effects of traditional stimulants, such as amphetamines.

There are several ampakines currently in development and undergoing clinical trials that may hit the market soon.

Ampakines can increase the size and duration of excitatory synaptic responses and induce the expression of neurotrophic factors as well.2Arai A, et al. A centrally active drug that modulates AMPA receptor gated currents, Brain Res. 1994 3Gary Lynch, et al. Ampakines and the threefold path to cognitive enhancement, Trends In Neuroscience. 2006

This indicates that ampakines can have a large effect on increasing certain kinds of brain activity and improving brain plasticity.

Ampakine Examples

There are a few commercial examples available or currently in development:

  • Sunifiram
  • Unifiram
  • Ampalex
  • Farampator
  • CX-717
  • LY-404187

These compounds all share similar mechanisms of action as ampakines, but their individual effects may vary somewhat.

What Does Ampakines Do?

Ampakines may in some respects be the strongest nootropics on the market. There are multiple cognitive functions it may improve.

Cognitive Enhancement

Christina Morillo
Ampakines may boost overall mental abilities

There is currently clinical evidence that ampakines can have a nootropic effect on cognition.

One preliminary study on rats shows ampakines enhanced their ability to focus and pay attention. On the other hand, it did show a decrease in object recognition memory.4Zheng Y, et al. Effects of the putative cognitive-enhancing ampakine, CX717, on attention and object recognition memory, Curr Alzheimer Res. 2011

Anther rats study reduced two measures of exploratory activity in aged rats but increased the speed of performance in a radial maze. The drug also caused substantially improved retention of spatial information.5C. Mike Davis, et al. A profile of the behavioral changes produced by facilitation of AMPA-type glutamate receptors, Psychopharmacology. 1997

There is evidence that ampakines are effective in enhancing synaptic responses, most likely by slowing deactivation. This could be the source of its cognitive enhancement.6Arai AC, et al. Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466, Mol Pharmacol. 2000

Learning and Memory

It seems that ampakines can selectively improve at least some aspects of memory.7Ingvar M, et al. Enhancement by an ampakine of memory encoding in humans, Exp Neurol. 1997 8Lynch G, et al. Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans, Exp Neurol. 1997

The ampakine BDP-12 can enhance synaptic responses even at lower levels.

This means that less activation is required to trigger a reaction, leading to quicker information transmission.9Arai A, et al. Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus, J Pharmacol Exp Ther. 1996

In other words, it effectively turned back the clock on the brains of older rats.10Granger R, et al. Facilitation of glutamate receptors reverses an age-associated memory impairment in rats, Synapse. 1996

The ampakine BDP-12 can reduce the amount of training needed for the formation of long-term memory in rats.11Larson J, et al. Facilitation of olfactory learning by a modulator of AMPA receptors, J Neurosci. 1995

BD12 was also shown to enhance AMPA-type glutamate receptors to selectively increase hippocampal spatial cell firing, which improves both acquisition performance and memory retention in middle-aged rats.12Granger, R, Deadwyler, S, Davis, M, et al. Facilitation of glutamate receptors reverses an age-associated memory impairment in rats, Synapse. 1996

Another study found that ampakines improved memory in three behavioral tasks.

Researchers concluded that ampakines could cross the blood-brain barrier and facilitate glutamatergic transmission in a way that enhances the encoding of memory across tasks.13U Staubli, G Rogers, G Lynch. Facilitation of glutamate receptors enhances memory, Proc Natl Acad Sci U S A. 1994

Although most of the memory studies on ampakines have focused on animal trials, one study looked at elderly adults.

The researchers found that the subjects who took ampakines scored twice as well on memory tests, closer to the memory capacity of young subjects.14Lynch G, et al. Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans, Exp Neurol. 1997


Schizophrenia is a hypoglutamanergic condition, meaning sufferers may experience lower rates of glutamate transmission.

So, upregulating this process could be a potential avenue to correct this deficit.15Sokolov BP. Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of “neuroleptic-free” schizophrenics: evidence on reversible up-regulation by typical neuroleptics, J Neurochem. 1998

The experimental ampakine BDP-29/CX564 greatly attenuated methamphetamine-induced hyperactivity, which was used as a model of psychosis.16John Larson, et al. Effects of an AMPA receptor modulator on methamphetamine-induced hyperactivity in rats, Brain Research. 1996

Ampakines enhanced the action of typical and atypical antipsychotics like haloperidol and clozapine synergistically. This result suggests that ampakines may be useful as an adjunct therapy with traditional drugs.17Johnson SA, et al. Synergistic interactions between ampakines and antipsychotic drugs, J Pharmacol Exp Ther. 1999

Similar results were also obtained in a study with 1-BCP.18Vanover KE. Effects of AMPA receptor positive modulators on amphetamine- and dizocilpine-induced locomotion, Eur J Pharmacol. 1997

In a human clinical study, the ampakine CX516 was added to clozapine in 4-week, placebo-controlled trial.

CX516 was tolerated well and was associated with moderate to large improvements in attention and memory compared with the placebo.

These preliminary results suggest that CX516 and similar compounds hold promise for the treatment of schizophrenia.19Goff DC, et al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia, J Clin Psychopharmacol. 2001


Ampakines may have a positive effect on mood, according to some preliminary research

One trial looked at ampakines on animal testing models commonly used to identify clinically useful antidepressants.

The preliminary findings indicate that biarylpropylsulfonamide-type ampakines, exemplified by LY392098, may represent a novel class of antidepressants.20Li X, et al. Antidepressant-like actions of an AMPA receptor potentiator (LY392098), Neuropharmacology. 2001

Another rat study also suggests that ampakines may have antidepressant activity.

The authors of this study noted that the rats that took the ampakines displayed less depressive behavior, even more so than the rats on traditional antidepressants.21Knapp RJ, et al. Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model, Eur J Pharmacol. 2002

Although there are no human trials on ampakines and depression currently, it seems to be a promising avenue for future research, and we look forward to seeing more studies.


Like the racetams from which they were derived, ampakines seem to have a neuroprotective quality.

One study saw a significant improvement in rats with methamphetamine-induced lesions when they were given ampakines CX546 or CX614.

Results were evident within 15 minutes of behavioral testing, indicating that ampakines may be particularly fast-acting neuroprotectives.22U.S Hess, et al. Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion, Neuroscience. 2003

How Ampakines Works In The Brain

ampakines nootropics
Ampakines work on the AMPA and NMDA receptors, which are some of the most prevalent receptors in the brain

Ampakines work on the AMPA and NMDA receptors, which are some of the most prevalent receptors in the brain
Ampakines and Aniracetam

Aniracetam is one of the most popular racetams for nootropics enthusiasts, with proven effects for memory and mood.

In 1990 researchers discovered they could selectively activate AMPA receptors via the ampakine aniracetam.23I Ito S Tanabe A Kohda H Sugiyama. Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam, Journal of Physiology. 1990

Aniracetam wasn’t designed specifically for the AMPA receptors, but this discovery provided a plausible explanation for a nootropic action for the first time.

However, aniracetam, despite its efficacy in some experimental settings, did not appear to have much clinical utility, in part because it is metabolized rapidly and requires relatively large doses.

So, using aniracetam as a point of departure, researchers began developing a separate family of drugs termed Ampakines. These drugs are the most widely studied group of AMPA receptor modulators, and they have been systematically tested for their effects on synaptic transmission, synaptic plasticity, activity in neuronal circuits, gene expression, and neuronal survival.

These efforts led to the discovery of IDRA-21, the alkyl-benzothiadiazide D1, S18986-1, and the pyridothiadiazines.

They also uncovered new compounds with distinct structural components such as PEPA and the biarylpropylsulfonamides, which are presently among the most potent AMPA receptor modulators

Ampakines can be orders of magnitude more potent than Aniracetam.24Arai AC, et al. Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466, Mol Pharmacol. 2000

The development of ampakines was largely guided by measuring their effectiveness in enhancing synaptic transmission rather than by their ability to block desensitization of AMPA receptor currents

How Much Ampakines Should I Take?

Ampakines are a class of nootropics, and dosage would depend on which particular one you are taking.

Ampakines Potential Side Effects

So far, initial trials saw no negative influence on heart rate, blood pressure or mood.

However, there is also evidence that ampakines might cause headaches, somnolence, and nausea.

There is also the possibility that shifting cortical neural plasticity in favor of long-term potentiation (long term memory) could lead to impairments in spatial memory and perhaps motor function.

Wrapping Up

Do you have questions about, supplementing with Ampakines? Do you have experience supplementing with Ampakines? Please share your thoughts in the comments below.

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About the author:

Erik Levi, FNTP

Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.

As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.

Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.

Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.

You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.

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