PRL-8-53 is a synthetic supplement with potential benefits for short term memory. More evidence is needed for its effects, since all current evidence comes from a study funded by the patent holder.
Sources and Structure
Methyl 3-(2-(benzyl(methyl)amino)ethyl)benzoate is a synthetic research chemical with the designation of PRL-8-53, created by the researcher Nikolaus R. Hansl who is also the patent holder. It is currently an unscheduled drug, which is a placeholder category for compounds not yet scheduled to be made illegal.
PRL-8-53 is a synthetic drug which is currently unscheduled.
Apomorphine is a dopamine agonist, and causes compulsive gnawing in rats. Combining PRL-8-53 with apomorphine can be used to assess the dopaminergic effect of PRL-8-53 via change in gnawing behavior. PRL-8-53 at 4mg/kg increased apomorphine-induced gnawing in rats, and was also effective in improving conditioned avoidance learning, indicating that PRL-8-53 is a dopamine agonist.
There is evidence in rats to suggest that PRL-8-53 is a dopaminergic agonist.
PRL-8-53 has failed to enhance methamphetamine's actions in rodents (which is commonly seen with tricyclic antidepressants), which suggests that PRL-8-53 does not strongly enhance norepinephrine and serotonin activity; it also failed to inhibit monoamine oxidase (MAO) (receptor subset not specified) at concentrations up to 1mM in vitro in rats.
PRL-8-53 has no known influence on MAO enzymes and does not augment methamphetamine.
Memory and Learning
Studies in rats have noted an increase in conditioned avoidance learning, with dose-dependent effects in the oral dosing range of 5-20mg/kg.
Oral ingestion of a single dose of 5mg PRL-8-53 120-150 minutes prior to cognitive testing noted that after a word recollection test (twelve monosyllabic words orally given to participants) that recollection measured 24 hours and 96 hours after testing was increased with PRL-8-53 relative to placebo. Overall improvements in recollection differed based on how many words were recalled under placebo, with the poor performers (six or less words) experiencing a 87.5-105% increase in recollection and the high performers (eight or more words) a 7.9-14% increase which failed to reach statistical significance; when controlling for subjects over the age of 30 only, a 108-152% increase was noted.
Acquisition rates (immediately after the test) failed to improve overall with PRL-8-53 relative to placebo aside from the subgroup that remembered less than six words under placebo, where a mild 18% increase in acquisition was noted and a 31.4% increase when assessing only persons over the age of 30.
The lone study in humans conducted by the patent holder has suggested relatively large increases in short term memory with single dose PRL-8-53. This information requires independent replication.
Safety and Toxicology
According to patent information, the LD50 of PRL-8-53 in mice is 860mg/kg bodyweight and side-effects leading up to this dose include a reduction in motor activity (also seen with high doses in the rat, which have an LD50 of 700-800mg/kg). The estimated ED50 for reducing motor activity in the mouse is 160mg/kg with minor reductions seen at 100mg/kg in the mouse but not rat and the lone human trial failed to note any interactions with motor control at the 5mg dosage. Injections of 150-200mg/kg in the mouse can induce convulsions, although lower doses do not.
The lone human study using a single dose of 5mg PRL-8-53 has failed to note any significant or minor side-effects associated with supplementation.
Based on very limited evidence, it seems that PRL-8-53 has a fairly large therapeutic threshold, but comprehensive toxicity studies in humans and rodents (looking at biochemical parameters) have not yet been undertaken.