Sunifiram is a popular and fairly new nootropic that belongs to the “ampakines” family. While most reports have led to consistent and positive results, many ampakines haven’t still been thoroughly studied.

Some clinical tests in animals have been done to study the effects of sunifiram. These tests have revealed positive effects associated with this nootropic’s use. However, there is a need of more thorough studies to determine its safety. Based on the limited studies, sunifiram seems to be well tolerated, but its long-term profile isn’t known yet.

Unlike most racetams that work mainly as cholinergic compounds, substances like sunifiram and unifiram work to attach themselves while stimulating the glutamate and AMPA receptors.

What Causes Glutamate Excitotoxicity?

Glutamate excitotoxicity results from an excess of glutamate in the body cells. As glutamate builds up in the cell, calcium ions are released. This in turn leads to the activation of enzymes, thereby damaging the cell.

Excitoxicity may result from a number of different factors. In fact, glutamate may act as an excitotoxin in your body. Glutamic acid is associated with glutamate and is commonly present as monosodium glutamate (MSG). MSG is a hazardous food additive used for improving taste and inducing a feeling of “fullness”, which becomes excitotoxic when taken in high doses.

Some studies have also shown that excitoxicity can be a consequence of brain damage. On the contrary, glutamate agonists are also associated with excitotoxicity. Agonists such as kainic acid and NDMA become excitotoxic when taken in high doses. Other factors like alcohol withdrawal can also cause excitotoxicity. This happens when the NMDA receptors get excessively agonized during the process.

Ampakines And Excitotoxicity

Most ampakines aren’t similar to glutamate agonists in terms of their method of action. Glutamate agonists tend to mimic glutamate’s properties for receptor-activation, which is what leads to excitoxicity. On the other contrary, most ampakines like sunifiram and unifiram tend to slow down this receptor activation. By slowing down the receptor currents, ampakines slow down the entire mechanism of AMPA receptor activation. In doing so, ampakines achieve the goal of improving memory as well as cognitive functioning.

It is important to note that the effects of these nootropics vary from study to study and ampakine to ampakine. This simply means that every ampakine has its own unique method of action. Some ampakines may show predominance in different regions of the brain, which is why, there’s a crucial need of thorough studies on the safety of each ampakine.

Some studies have shown that ampakines like sunifiram may play an active role in preventing against the excitotoxicity induced by these substances themselves. Although it has been observed that the AMPA receptor’s intense activation causes this excitoxicity, activation results in the transduction of defensive protein kinases as well. Some studies have revealed that the activation of certain protein kinases may help in offering protection against neurotoxicity. This means, if certain ampakines are able to affect the kinases pathways, they may actually serve as neuroprotective substances.

So, What Can Be Concluded?

Based on past studies, it can be concluded that ampakines like sunifiram and unifiram are safe to use. But, it’s equally important to realize that these substances carry some risks. Science may help in getting a better understanding of glutamatergic transmission, which is why, it is best to use these nootropics with care while making sure that you don’t go beyond the recommended dosage.

Lastly, be cautious while using ampakines in combination with other substances. Just because a new nootropic seems to be safe by itself, doesn’t mean it will not become toxic when used in combinations. In fact, certain ampakines may enhance their excitotoxicity when combined with other substances.