PRL-8-53
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.
Last Updated:September 28, 2022
1.
Sources and Structure
1.1
Sources
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[1] who is also the patent holder.[2] 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.
2.
Neurology
2.1
Dopaminergic Neurotransmission
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.[1]
There is evidence in rats to suggest that PRL-8-53 is a dopaminergic agonist.
2.2
Other Mechanisms
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.[1]
PRL-8-53 has no known influence on MAO enzymes and does not augment methamphetamine.
2.3
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.[1]
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.[3] 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.[3]
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.[3]
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.
3.
Safety and Toxicology
3.1
General
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[2] (also seen with high doses in the rat, which have an LD50 of 700-800mg/kg[1]). The estimated ED50 for reducing motor activity in the mouse is 160mg/kg[2] with minor reductions seen at 100mg/kg in the mouse but not rat[1] and the lone human trial failed to note any interactions with motor control at the 5mg dosage.[3] Injections of 150-200mg/kg in the mouse can induce convulsions, although lower doses do not.[1]
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.[3]
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.