Summary

PRL-8-53 (chemical name Methyl 3-(2-(benzyl(methyl)amino)ethyl)benzoate) is a synthetic nootropic compound discovered in 1972 and patented in 1975 by the late Dr. Nikolaus Hansl, a neuropharmacologist at Creighton University in Omaha, Nebraska.

Preliminary animal tests indicated that the compound was both safe and significantly nootropic, boosting avoidance learning in rodents with no adverse effects. But the real interest in PRL-8-53 was sparked by a 1978 study on human volunteers, which showed that a single dose of the compound could improve word retention scores by more than 200%.

Interest in the compound was further fueled by comments from author and longevity specialist Durk Pearson, who was quoted in ‘High Frontiers’ as follows: “PRL-8-53 is a terrific memory enhancer. Normally you can memorize about seven or eight digits just by looking at them for a second. PRL-8-53 gives the average person a memory span of about 21 to 22 digits.”

The sole human study on PRL-8-53, which was funded by Hansl shortly after he patented the compound, strongly supports the drug’s potential as a nootropic. The study measured word retention in a group of 30 healthy volunteers between 24 and 86 years of age. While participants who had good baseline word retention scores showed little improvements after taking PLR-8-53, participants who had low initial scores or who were over 30 demonstrated major improvement following a 5mg dose of PLR-8-53, in many cases more than doubling their rate of recall.

No adverse effects were noted in the human study.

Anecdotal evidence appears to support claims for PRL-8-53’s safety and nootropic capabilities, but it is still considered an experimental drug because of limited testing.

PRL-8-53 is currently an unscheduled drug and can be legally purchased in the US.

Benefits and Effects

Memory enhancement – The older subjects in the only human study on PRL-8-53 demonstrated significant improvements in memory after taking a single 5 mg dose. The double-blind study used word memorization as a measure, testing the participants’ ability to recall a list of 12 one-syllable words, first to establish a baseline and then again after ingesting PRL-8-53 or a placebo. The subjects were tested on their ability to recall the words 24 hours after hearing them and then again one week later.

The study results indicate that participants who had higher baseline scores showed the least improvement after ingesting PRL-8-53, while subjects who had demonstrated poorer initial memory or who were over 30 years of age showed significant improvement in recall. In an article on the test, Hansl described the effect on the older participants as follows:

“This group was age 30 or older. As might be expected, rote memory did not come as easily to this group as it did to the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24 hour test and 152% for the one-week recall.”

Many individual nootropic users who have tried PRL-8-53 confirm its memory-boosting effects, in some cases comparing it to a more powerful version of other nootropics such as nefiracetam and Noopept.

How it Works

PRL-8-53’s exact mechanisms of action are not well understood, but it is believed to regulate the brain’s production of and response to several crucial neurotransmitters. In his reports on human and animal studies, Hansl indicated that PRL-8-53 potentiates dopamine, partially restricts production of serotonin, and enhances the brain’s response to acetylcholine. Though Hansl’s research report on the 1978 human study suggests those actions, it does not clearly delineate the mechanism of action.

The fact that older subjects saw the most nootropic benefit from taking the drug supports the concept that dopamine modulation plays a significant role in PLR-8-53’s effects. Upregulating the normal age-related lessening of dopamine production that is associated with cognitive decline could have a significant positive impact on both learning and memory.

In a 1979 article entitled “Learning and Memory Improvement Through Chemistry: Dream or Reality in the Offing?” Hansl said “PRL-8-53 has been shown to augment responses to noradrenaline in the animal model both peripherally and centrally. Therefore, it seems reasonable to assume that a similar function may be present in humans. Translated into behavioral effects, it implies that this drug is also capable of facilitating the conversion of short-term to long-term memory, causing an increased storage of informational code.”

In the same article, Hansl says, “PRL-8-53 has been shown to enhance the response to acetylcholine, the response being quantitatively similar over a considerable dose range, excluding the likelihood of accidental overdosing.”

Hansl further said “The drug is not a stimulant, and in the experimental animal toxicity appears only after it is given a dose more than one thousand times as large as the projected human dose. In summary, we now have a potentially useful drug that will boost a specific chemical system in the brain, the cholinergic system, and thereby improve our ability to recall, to retrieve information from a pre-existing information pool.”

Dosage

The only human study on PRL-8-53 was based on the ingestion of a single 5 mg dose. There is no data on the effectiveness or potential toxicity of any other dosage in humans.

Stacking

Due to the limited understanding of PRL-8-53’s mechanism of action, it may be advised to avoid stacking it with other nootropics.

Side Effects

No adverse effects from a single 5 mg dose of PRL-8-53 were observed in the human study. Animal studies suggest that the compound has a high therapeutic threshold, but the evidence is very limited because no comprehensive toxicity studies have been completed.

Keep in mind, this is a highly experimental research chemical, therefore caution is advised.

Where to Buy

Because PRL-8-53 is an experimental nootropic, you’ll want to be especially certain that you are actually getting the authentic compound that you’ve ordered.

The best way to ensure you get pure PRL-8-53 is to stick to reputable nootropic vendors. We recommend NootropicsDepot.com for buying PRL-8-53 for both their reasonable pricing and the fact that all their nootropics are tested for purity.

Closing Thoughts

PRL-8-53 is an intriguing if largely unexplored synthetic nootropic that many believe will eventually prove to be an invaluable smart drug.

Though it triggered strong interest when it was introduced 40 years ago, research on its possibilities came to a halt after a few animal tests and a single human study; little has been learned about it since the study that sparked such strong interest in its potential as a memory enhancer.

At this time there does not appear to be any ongoing research on the compound, but curiosity about its possibilities continues and is considered to be one of the best short-term memory boosters on the market by nootropic enthusiasts.