Unifiram (CAS# 272786-64-8) is a substance that was reported in year 2000 to have similar properties to piracetam but more potent in a mouse passive avoidance test [1]. However, unifiram has shown pro-cognitive effects for mice by preventing amnesia induced by scopolamine (muscarinic antagonist), mecamylamine (nicotinic antagonist), baclofen (GABA-B agonist), clonidine (alpha-2 agonist), NBQX (AMPA antagonist) in passive avoidance test [2]. The limitation of these methods is that nootropic compounds such as unifiram (and piracetam) have usually*** failed to show memory facilitation without induction of these amnesia-inducing compounds. However, in the context of social learning task the memory facilitiation was detected when the test was prolonged over time that is usually required for rats to forget. Unifiram did not cause overt modification of animals’ behavior, impairment motor coordination on rotarod test or alteration of exploratory behavior on hole-board test [2]. The exact mechanism of action of unifiram is unknown. It has been observed that unifiram increases the release of acetylcholine (and associated pain tolerance), antagonizes kynurenic acid (endogenous glutamte antagonist) at AMPA receptor (rather than NMDA receptor) and slightly amplifies excitatory currents (fEPSP). However, unifiram does not bind to the same receptors that are attacked by amnesic compounds (scopolamine, mecamylamine, baclofen, clonidine, NBQX, kynurenic acid), and hence, its mechanism is indirect and unknown. It has been suggested that the mechanism of unifiram is similar to that of ampakines or related to desensitization of AMPA receptors [2]. . Other authors have found in a mouse study that the effect of unifiram may be allosteric modulator of NMDA receptor on glycine binding site (antagonized by gavestinel) and thus enhance long term potentiation that facilitates memory[3]. Conversely, the same authors found that unifiram did not show antidepressant properties as assessed by tail supension test. While unifram has (or had?) potential for cognitive enhancement and it seems to have very low short-term toxicity, it is not patented, long-term toxicity is unknown, and human studies have not been performed despite unexpected interest from lay persons interested in cognitive enhancement[4].

1. https://www.ncbi.nlm.nih.gov/pubmed/10821709.
2. https://www.ncbi.nlm.nih.gov/pubmed/16834757
3. https://www.ncbi.nlm.nih.gov/pubmed/23295391
4. https://www.ncbi.nlm.nih.gov/pubmed/25831025