Nootropics are substances that facilitate learning without toxic effects or significant alteration of behavior (including sedation and stimulation). Traditional nootropics are selected number of plants such as Withania somnifera (ashwagandha) or Panax ginseng. Classical nootropics are piracetam and its similar but more potent analogues that are characterized by their ability to protect normal brain function under chemical stress caused by substances that cause amnesia or delirium. In addition to herbal and classical nootropics, there are a few other research chemicals that may deserve attention.
PRL-8-53 was found to have very low toxicity in animal studies. In humans, the researchers observed enhancement of rote verbal memory in a study conducted in the 1978 but since then PRL-8-53 has been not researched further. Surprisingly, it seems that some people actually use that research chemical: according to Reddit nootropics survey, PRL-8-53 was considered as the best memory enhancer.
NSI-189 was found to increase hippocampal neurogenesis, long-term mood and memory in humans with a good safety profile. While NSI-183 has been researched in humans in multiple studies, its exact mechanism of action is more or less unknown. The latest (2019) study of NSI-189 is currently Phase II clinical placebo-controlled and randomized study that showed antidepressant and pro-cognitive effects while well-tolerated in 220 patients with depression.
Unifiram facilitates memory in rats, and its potency is orders of magnitude higher than that of piracetam. Hence, its effective dose is much lower as well. Its mechanism of action is relatively unclear: it does not activate glutamate receptors itself but seems to desensitize AMPA receptors and modulate NMDA receptors according to the latest research that does not, unfortunately, include human studies.
Fluorenol is almost completely unresearched chemical biologically. However, it is a metabolite of modafinil in rats, and it is a simple molecule. According to chemical screening, its predictable side effects may be that it interferes with the effects of testosterone and it may reduce endurance due to interference with mitochondria. However, the results of a rat study did not show overt toxicity to the rodents and it may well be speculated that it is a more specific wakefulness-promoting agent that has even lower probability to be habit-forming.