AMPAkines are benzamide compounds, which are a class of agents who modulate the activity of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in post-synaptic neurons (Samartgis et al., 2012). Aniracetam, piracetam, sunifiram, unifiram, cyclothiazide, CX717, IDRA-21, CX516, CX546, and BDP are some of the drugs classified as AMPAkines. They are also referred to as nootropics or cognitive enhancers because of their effect on neurotransmission that, in turn, has been shown to positively affect memory and learning.


AMPAkines modulate AMPA receptors in the hippocampus – the part of the brain responsible for explicit memory and the processes of encoding, pattern completion, and pattern separation (Tamminga, Stan & Wagner, 2010). The hippocampus has densely-packed neurons containing glutamate – a neurotransmitter. AMPA receptors, on the other hand, enable rapid excitatory transmissions from one neuron to another. Neurotransmission occurs at the synapse or the junction between two neurons and involves the inward and outward movement of ions across channels in the cell membrane mediated by a neurotransmitter (Barnes, 2013). AMPA receptors interact with glutamate.

AMPAkines act to prolong the time the ion channels are open thereby enhancing excitatory neurotransmission facilitated by glutamate (Silverman et al., 2013). AMPAkines also induce synaptic plasticity permitting the synapses to adapt to greater and prolonged activity. Neurons with AMPA receptors show potentiated calcium signaling resulting in increased single-channel conductance of electrical signals and therefore, reduced receptor deactivation (Montogomery, Kessler & Arai, 2009). This is also referred to be as long-term potentiation. The magnitude of these actions is significantly greater – up to be ten-fold with CX546 – in pyramidal neurons found in the hippocampus and cerebral cortex.
Ampakines Effects


The action of AMPAkines has several effects. Enhanced memory and learning are seen in tasks involving rats, chicks, and non-human primates (Samartgis et al., 2012; Silverman et al., 2013). This is because long-term potentiation and synaptic communication such as induced by the drug is thought to be the underlying neurophysiological mechanism in learning and the formation as well as consolidation of memory (Kariharan et al., 2008). Benefits have also been observed in humans. Daily doses of 400-mg piracetam administered to healthy college students showed an improvement in verbal memory after the 14-day trial compared with the placebo group (Samartgis et al., 2012). Task accuracy and memory also improved among cognitively-impaired chronic alcoholics who took 1,200 mg doses of piracetam twice a day.

In addition, preliminary studies have shown the potential benefits of AMPAkines in patients with autism, Huntington’s disease, and Angelman syndrome. Considering that AMPAkines improve two areas of cognitive ability, Silverman et al. (2013) used CX1739 and CX1837 in a mouse model of autism. The mice showed deficits in sociability reflective of impairment in social cognition – a person’s ability to understand himself and other people. The study showed a reversal in the sociability deficit, although it remains to be established if synaptic mechanisms in the regulation of social cognition were indeed involved.

Ampakine Coluracetam Capsule

Baudry et al. (2012) also employed a mouse model but of Angelman syndrome, a hereditary and incurable disorder where patients manifest with deficits in both long-term potentiation and learning. The mice received CX929 injections twice a day for 5 days or placebo. Neurotransmission simulations were used to determine the synaptic response which showed that in the AMPAkine group, long-term potentiation was stable and comparable with those of usual mice. Scores in long-term memory in the AMPAkine group were related with those of common mice while scores were 50% lower in the placebo group suggesting a possible role for CX929 in patients with the syndrome.

Simmons et al. (2011) also employed CX929 in a mouse model of Huntington’s disease to determine the effects on brain degeneration and locomotion. Genetic mutation causes reduced production of brain-derived neurotrophic factors (BDNF), a protein that aids in the regulation of synaptic plasticity and the survival of neurons. The study builds on previous findings that AMPAkines reduced defects in synaptic plasticity in mouse models of Huntington’s disease. The authors found that the drug averted reductions in the striatal area of the brain indicative of neuron preservation in the AMPAkines group. Enhanced motor performance was also noted in the mice that received AMPAkines.


AMPAkines are new drugs, and most are still being investigated. Given the mechanism of action shown in animal models and boosted by the positive results of the study on piracetam use among students, the use of AMPAkines as nootropics or purely for cognitive enhancement among healthy people arose (Madan, 2014). Nootropic use is also referred to as cosmetic use or off-label use since these drugs were originally or were being developed as treatments for disease. Piracetam, for instance, is indicated for dementia and other cognitive disorders, although the high cost of the drug and effectiveness that has not been firmly established to make it less preferred compared with older drugs (Winblad, 2005). Studies do show, however, that college students are taking AMPAkines, mainly piracetam, to boost their academic performance through perceived enhancements in vigilance, concentration, memory, and learning without any apparent side effects (Madan, 2014).


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