On April 3rd of this year, the FDA banned the use of DMAA (1,3 dimethylamylamine) in supplements, claiming that it is not a dietary ingredient. Though some companies will fight the ban – based on the fact that DMAA can be found naturally in some plants – the FDA will get its way and the ban will be upheld. As a result, products containing DMAA will start disappearing from the shelves. Due to DMAA’s effectiveness at powering mind and body through even the toughest workouts, the search is on for the next nootropic amine. Luckily, we have already found it.
N-phenethyldimethylamine (NDMPEA) is a powerful neuroenhancer that has many structural similarities to DMAA and other neuroactive amines, such as phenethylamine (PEA). In chemistry, function follows structure, and both structure and function are related to charge. Just like amphetamines, each of these molecules has a nitrogen atom at one end – an electron donor – that binds to dopamine receptors, a neurotransmitter involved in mood and energy, and specifically reward-motivated behavior. A molecule’s affinity for dopamine receptors is controlled by how easily the nitrogen can donate its electrons, which is determined by how the electrons are “shared” by the rest of the molecule. DMAA is effective because the rest of the molecule doesn’t want to share the electrons, so the nitrogen can easily donate them and be active. With NDMPEA and PEA, their total molecular structure will share the electrons, making the nitrogen slightly less active and the molecules slightly less potent. However, NDMPEA is much better than many of its counterparts for a different structural reason.
Many amine-containing molecules, from supplements to pharmaceutical and recreational drugs, do not last very long in the system due to the enzyme monoamine oxidase. Monoamine oxidase cleaves off the nitrogen atom from amines, rendering them inactive and available for elimination from the body. Therefore, longevity of activity for amines results from a structural protection of the amine. With PEA, the effect is noticeable, but very short-lived, because the nitrogen is not protected. On the other hand, the dimethyl of NDMPEA refers to two methyl (carbon) groups that are attached to the nitrogen, conferring protection. Therefore, NDMPEA is much more similar to DMAA in its potency and longevity (DMAA is similarly protected with a methyl group one carbon away from the nitrogen).
One more aspect of how structure leads to better functioning is lipophilicity, or fat solubility. Cell membranes are made of fat, so molecules that are more fat-soluble are better able to cross the blood-brain barrier and bind to receptors on target tissues. The methyl groups on NDMPEA make the molecule much more lipophilic and increase density and effectiveness at the receptor level. Delivery of molecules to target tissue is essential for bioactivity – there are many supplements in the past that have the mechanisms to be effective, but oral consumption does not increase levels of the compound in the target tissue, whether that is the muscle or the brain. Therefore, the lipophilicity of NDMPEA may make all the difference in establishing it as the go-to amine for stimulation of the central nervous system.
Will NDMPEA Get Banned Like DMAA?
Now that we have addressed how it works, it is time to look at the elephant in the room: how soon will it be banned? They did it with DMAA, why won’t NDMPEA be next? We believe that the documentation is already in place so that the FDA will not be able to ban NDMPEA, and it revolves around GRAS status. GRAS status, or Generally Recognized as Safe, means that a food additive is compliant with the FDA because it has been adequately shown to be safe. NDMPEA is already used as a flavoring, according to the FDA database EAFUS, which stands for Everything Added to Food in the United States, and has existing documentation that it is safe for use, according to the “Evaluation of Certain Food Additives” by the World Health Organization. Therefore, it will be difficult for the FDA to disqualify their own documentation and rule the molecule unsafe for use at any time in the future.
In addition, NDMPEA has been found in nature. As mentioned at the beginning of the article, being found in nature is not sufficient for the FDA (see DMAA), but there are important differences between the two cases. Much of the discussion in the courts surrounding the DMAA ruling have to do with the fact that the amounts of DMAA in geranium stems is miniscule and that there is little evidence of DMAA being extracted from geranium for use in supplements. In contrast, NDMPEA is found in Eria jarensis and is often used in supplements as whole plant Eria jarensis extract. Additionally, documents from the World Health Organization maintain that NDMPEA is also found in shrimp, in case further support is needed.
In conclusion, NDMPEA is an amine-containing CNS stimulant with the potency, longevity, and lipophilicity to make it a natural successor to DMAA. It will be difficult for the FDA to ever ban it, since they have public documentation illustrating its safety as a food additive for flavoring purposes. Additionally, it is naturally-occurring and utilized in supplements as a whole plant extract. The clock is ticking for DMAA, so why not try the next best thing – NDMPEA!