RGPU-95 (p-Cl-Phenylpiracetam) is an 5x – 10x more potent derivative of the nootropic compound Phenylpiracetam.

RGPU-95 is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.

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RGPU-95 (p-Cl-Phenylpiracetam) Nootropic Powder

RGPU-95 (p-Cl-Phenylpiracetam) is an 5x – 10x more potent derivative of the nootropic compound Phenylpiracetam.



CAS Number 213178-69-9
Other Names 1-Pyrrolidineacetamide, 4-(4-chlorophenyl)-2-oxo; RGPU-95
Molecular Formula C₁₂H₁₃ClN₂O₂
Molecular Weight 252.7
Purity ≥99% Pure (LC-MS)
Liquid Availability 30mL liquid (10mg/mL, 300mg bottle)
Powder Availability 1 gram

 5 grams

Storage Store in cool dry environment, away from direct sunlight.
Terms All products are for laboratory developmental research USE ONLY. Products are not for human consumption.



What is RGPU-95?

RGPU-95 is a structural analogue of phenylpiracetam, a nootropic compound widely known for its antidepressant and anxiolytic effects. The development of RGPU-95 was the result of a targeted search for N-carbomail-methyl-4-para-chloro-phenyl-2-pyrrolidone that revealed how modification of the structure of phenylpiracetam enhances the efficacy, specificity, and bioavailability of the compound while instances of side effects and toxicity are decreased. Phenylpiracetam is derived from piracetam by adding a phenyl ring to position 4 of the 2-oxopyrrolidine ring [1].

Originally, phenylpiracetam was synthesized in 1983 by the Soviet Union in order to help their Cosmonauts deal with the stress of space travel. According to the manufacturer, phenylpiracetam’s improved lipophilicity allows for faster and more effective absorption. With the addition of the phenyl ring to the pyrrolidine ring, both an R and an S isomer of phenylpiracetam exist. When comparing the R-isomer and S-isomer it is clear that the R-isomer is more active when it comes to cognition and stimulation. However, the racemic mixture of the isomers is more commonly sold than the R-isomer alone. While the racemic mixture is successful at increasing cognitive functioning, it is not clear if there are any significant stimulatory benefits [1].


Main Research Findings

1) RGPU-95 elicits significant antidepressant and anxiolytic effects in male rats and, to a lesser extent, female rats.

2) R-phenylpiracetam is involved in neuroprotective and anti-inflammatory activity in models of inflammation in male mice.


Selected Data

1) The research experiment conducted by Tyurenkov et. Al examined how treatment with RGPU-95 and phenylpiracetam affects anxiety-depressive behavior in male versus female rats. 50 female and 50 male Wistar rats weighing between 250-280 grams were included in the study and maintained in standard vivarium condition including a 12 hour light/dark cycle, consistent room temperature, and food and water provided ad libitum. All animals included in the study were obtained from the Federal State Unitary Enterprise “Rappolovo Laboratory Animal Nursery” of the Russian Academy of Medical Science, while kept in accordance with the rules of laboratory practice in the Russian Federation and Order of the Ministry of Health. The test subjects underwent an open field test in order to observe the effect of RGPU-95 on spontaneous individual behavior. The anxiolytic properties of both compounds were measured by placing the test subjects into classic models of anxiety such as the Vogel variant and the “elevated cruciform maze” test. Additionally, the antidepressant effects of RGPU-95 was investigated through the Porsolt test of unavoidable forced swimming which is typically used as a model of stress-induced depression [2].

The compound was administered to both male and female test subjects in equimolar concentrations of doses of 1/10 the molecular weight. For RGPU-95 this corresponded with a dose of 25 mg/kg. All substances used in the study were synthesized at the Department of Organic Chemistry of the Herzen Russian State Pedagogical University. 1 mg/kg of diazepam and 15 mg/kg of melipramine were also administered to the test subjects as positive control agents. RGPU-95 was found to be not completely soluble in water so the research team diluted the compound in 2% starch mucus to create a uniform suspension. Animals administered the control treatments also received a solution of starch mucus in an equivalent volume in order to rule out an error related to the presence of starch mucus. The test subjects were orally administered the combination of active treatment and starch mucus or positive control and starch mucus approximately 60 minutes before the tests took place. All statistical analysis was completed using non-parametric testing, including Mann-Whitney U-test, Kruskal-Wallis rank one-factor analysis, Dana criterion for multiple-statistical comparison, and chi-square tests [2].

2) RGPU-95 is a derivative of phenylpiracetam and has many of the same benefits. That being said, in addition to its antidepressant and antianxiety effects, the research team of Zvejniece et. Al examined the potential neuroprotective and anti-inflammatory effects of R-phenylpiracetam. The study utilized 246 ICR mice aged 8-10 weeks and weighing 23-25 grams. All subjects were housed under standard conditions and provided food and water ad libitum while housed in individual cages. Each cage was ventilated and contained a bedding of shaving wood chips, nesting materials and wooden blocks, as well as a polycarbonate safe harbor mouse retreat for enrichment purposes. The doses of R-phenylpiracetam were selected based on the finding of initial research performed that found doses of the compound at 10 mg/kg and 50 mg/kg had the potential to significantly increase locomotor activity. All test subjects were randomly assigned to a treatment group while the investigators were blinded to the group assignment [3].

Concentrations of R-phenylpiracetam in the brain and plasma was measured through the use of ultra-performance liquid chromatography-tandem mass spectrometry. The compound was administered both intraperitoneally and perorally to the test subjects at a dose of 50 mg/kg at 15 minutes, 30 minutes, and 1, 2, 4, 6 and 24 hours prior to decapitation of the animals and the collection of plasma and brain tissue. Nine groups consisting of 4 mice each were randomly assigned. Heparin-coated tubes were used for blood collection and underwent centrifugation in order to separate the plasma. This procedure was followed by the removal of brain tissue; two samples were collected from each animal as the brains were split into the right and left hemispheres. The brain tissue was homogenized via a Cole Parmer 130-W ultrasonic processor. The resulting homogenates were repeatedly centrifuged in order to obtain relevant supernatants that were further combined and frozen until the research team was ready to thoroughly analyze them. An acetonitrile/formic acid mixture was used to prepare the samples by deproteinization, followed by centrifugation and transfer of the supernatants to UPLC vials used for mass spectrometry analysis [3].

Inflammatory gene expression was stimulated in the test subjects through an intraperitoneal injection of 20 mg/kg of LPS. A control treatment or an active treatment of R-phenylpiracetam at doses of 50 mg/kg were injected simultaneously with LPS on opposite sides of the animals. Additionally, edema in the paws of the test subjects was induced through an intraplantar injection of carrageenan. Prior to the injection all test subjects were perorally administered saline, R-phenylpiracetam in doses of 10 mg/kg, 25 mg/kg, or 50 mg/kg, or 10 mg/kg of indomethacin for 7 days. On day 7 the animals received their treatment approximately 60 minutes before carrageenan was injected. Each group of animals either received an intraplantar injection of 40 uL of saline of 40 uL of 2% carrageenan. Paw value was measured using a plethysmometer and was recorded prior to the carrageenan injection and 2, 4, 6, and 24 hours after the injection. While measuring paw edema, the research team marked the right hind paw of each subject in order to ensure equal immersion in the measurement chamber of the plethysmometer. The same experimenter always measured the same group of test subjects while remaining blinded to the treatment groups.

An electronic von Frey anesthesiometer was used to measure the withdrawal threshold of the right hind paw in response to a mechanical stimulus in order to assess mechanical allodynia. In this experiment the withdrawal threshold was defined as the average force in grams required to cause withdrawal of the stimulated paw over three trials. The test took place 7 hours after carrageenan was injected and began by placing the mice on a metallic grid floor in an individual observation chamber where they were allowed to acclimate to the new setting for 10 minutes. The von Frey filament was applied to the surface of the right hind paw and stimulus was applied until withdrawal occurred and the measurement was recorded [3].

Prior to the initiation of the formalin-induced paw-licking test, the animals received peroral administrations of either saline, R-phenylpiracetam in doses of 10 and 50 mg/kg, or a 50 mg/kg dose of S-phenylpiracetam, for 7 days. On day 7 the treatments were administered to the test subjects, followed by an 30 uL intraplantar injection of formalin in the right hind paw 60 minutes later. The mice were then placed in a Plexiglass observation chamber while the total licking time of the hind paw for each subject was recorded with a stopwatch. The recorded times were then quantified in subsequent 5-minute intervals over a 60 minute period. The first phase of the test lasted 5 minutes and began by immediately recording the time spent licking, while the second phase of the test lasted approximately 35-40 minutes and started 15-20 minutes after the injection of formalin [3].



1) The results of the “open field” test all subjects went through, female test subjects of the control group displayed higher indices of both exploratory and locomotor behavior in comparison to the male subjects. There was also a notable increase in the number of acts of short-term grooming in the female control subject group, which indicates a significant level of emotional discomfort and tension. Overall, females were shown to have higher levels of anxiety than males while RGPU-95 did not have a dramatic effect on exploratory or locomotor behavior. However, phenylpiracetam was found to increase exploratory and locomotor behavior in both male and female rats while under the condition of “situational novelty” stress. More specifically, exploratory, or orientation activity increased more in male test subjects while locomotor activity was increased more in female test subjects when treated with phenylpiracetam. It is also important to mention that treatment with phenylpiracetam increased the number of exits to central zones while decreasing the number of short-term “anxious” grooming acts [2].

The female test subjects in the positive control groups exhibited a higher level of anxiety than the male test subjects in the “elevated cruciform maze”. The females spent less time in the open arms of the maze and entered them less than the males leading to almost no standing and no hanging occurring in the open arms of the test. Both of the experimental treatments, RGPU-95 and phenylpiracetam, were shown to experience an increase in the number of stands and exits to the open arms of the maze, the amount of time spent in the arms, and the number of hang-ups from the open sleeves in both male and female test subjects. The male test subjects administered RGPU-95 experienced a greater anxiolytic effect than those receiving phenylpiracetam [2].

In addition to the “elevated cruciform maze”, Vogel conflict conditions revealed that female test subjects were more susceptible to anxiety based on their food and defensive behavior. Overall the females were shown to stay away from the drinker for longer periods of time than the males and ultimately made fewer, low risk attempts to reach the drinker. The positive control compound, diazepam, as well as both phenylpiracetam and RGPU-95 were found to decrease anxious behavior in the animal test subjects and had an overall anti-conflict anti-anxiety effect in this model for both male and female rats. RGPU-95, phenylpiracetam, and diazepam all had a significant effect on the latency of approach in the female subjects while also increasing the number of approaches to satisfy drinking motivation in the male subjects. These observations indicate a greater expression of the anxiolytic effect in the male animals that are naturally less prone to anxiety. Overall, the anti-anxiety effects of RGPU-95 were shown to be superior to those of phenylpiracetam, but still inferior to diazepam.

Similar to the results of the anxiety-inducing test, results of the Porsolt test of unavoidable force swimming found that the female test subjects in the control groups exhibited a greater degree of depressive behavior. These results were determined by their longer total duration of immobilization, a shorter latency of period of immobilization, and a lower number of jumps. RGPU-95, as well as phenylpiracetam and melipramine were shown to cause a significant increase in the immobilization latency period, as well as a decrease in total immobilization time in both males and females. These findings indicate the antidepressant activity of the compounds. RGPU-95 was shown to be superior to phenylpiracetam while eliciting similar effects as melipramine [2].

2) The initial results of the study conducted by Zvejniece et. Al reported that R-phenylpiracetam is capable of crossing the blood-brain barrier. The compound was detectable in the brain tissue sample approximately 15 minutes after a single peroral or intraperitoneal injection. R-phenylpiracetam reached peak concentrations in the brain 30-60 minutes after the intraperitoneal injection and 60-120 minutes after peroral administrations. After the peroral and intraperitoneal injections of the compound, the maximal concentrations of R-phenylpiracetam in the brain tissues were 28 ug/g and 18 ug/g, respectively. After 24 hours the compound was no longer detectable in the tissue samples. In terms of the plasma samples, R-phenylpiracetam was detected 15 minutes after a single peroral and intraperitoneal injection. Maximal concentration of the compound in plasma was identified 15-30 minutes after a single intraperitoneal injection and 60 minutes after peroral administration. These recorded times correlated to a maximal concentration of 45 ug/mL after the intraperitoneal injection and 24 ug/mL after peroral administration. After 24 hours R-phenylpiracetam was still detectable in the plasma at 0.05 ug/mL with both peroral and intraperitoneal administration [3].

Figure 1: A) Concentration of R-phenylpiracetam in samples of brain tissue. B) Concentration of R-phenylpiracetam in plasma samples.

When examining the anti-inflammatory effects of the compound, body temperature was assessed and recorded in all groups before and after inflammation-inducing injection of LPS. Prior to injection, the body temperature was similar across all groups, however, 6 hours after injection body temperature of the experimental groups significantly decreased in comparison to the temperature of the subjects included in the control group. Injection of LPS was also related to a significant increase in the expression of inflammatory genes such as IL-1 beta, TNF-alpha, and iNOS by 75%, 73%, and 65%, respectively. Inflammatory gene expression in the experimental group administered R-phenylpiracetam did not significantly differ from expression in the control group. The researchers thought it was important to note that pretreatment with S-phenylpiracetam led to a slight reduction in the expression of IL-1 beta and TNF-alpha in comparison to expression in the LPS control group. However, the S-phenylpiracetam experimental group had significantly higher levels of inflammatory gene expression than the saline-treated test subjects. There was also no noticeable difference in LPS-induced iNOS gene expression in the test subjects treated with R-phenylpiracetam versus S-phenylpiracetam [3].

Figure 2: Changes in inflammatory gene expression in response to different experimental treatments

Edema of the paw was measured by increase in paw size due to inflammation caused by an intraplantar injection of carrageenan. Carrageenan was shown to significantly increase incidences of paw edema in a time-dependent manner, in comparison to the saline-treated control group. These findings were solidified by two-way repeated-measures ANOVA statistical analysis that reported the time-dependent attenuation of carrageenan-induced edema. When administered in doses of 50 mg/kg, R-phenylpiracetam was shown to significantly reduce paw edema at 2, 4, and 6 hours after injection of carrageenan by 60%, 40%, and 45%, respectively. The 10 mg/kg and 25 mg/kg doses of the compound did not reduce paw volume. A 10 mg/kg dose of indomethacin was shown to reduce paw edema at 4 and 6 hours after injection of carrageenan by 36% and 45%, respectively. These findings were confirmed by a two-way repeated-measures ANOVA that confirmed administration of both R-phenylpiracetam and S-phenylpiracetam at 50 mg/kg reduced formation of edema in response to an injection of carrageenan.

Figure 3: A) Percent increase in paw volume. B) AUC displaying increases in paw edema.

Results also reported that pretreating the subjects with R-phenylpiracetam was able to significantly decrease paw edema at 2 and 4 hours after injection of carrageenan by approximately 50%. Pretreating the subjects with S-phenylpiracetam was able to significantly decrease paw edema 4 hours after injection of carrageenan by approximately 34%. Finally, pretreating the subjects with indomethacin was able to significantly decrease paw edema at 4 and 6 hours after injection of carrageenan by approximately 37%. Mechanical sensitivity was determined by the electronic von Frey filament test. Withdrawal threshold was shown to significantly reduce 7 hours after the carrageenan injection in comparison to the control group that received an intraplantar injection of saline. Overall, the results found that peroral administration of 50 mg/kg doses of R-phenylpiracetam and 10 mg/kg doses of indomethacin 60 minutes prior to the carrageenan injection, led to a reduction in mechanical sensitivity by 35% and 40%, respectively [3].

Figure 4: Changes in mechanical withdrawal threshold in response to administration of different experimental treatments.

Finally, the formalin-induced paw-licking test examined the antinociceptive effects of both R-phenylpiracetam and S-phenylpiracetam. Licking and shaking of the formalin-injected paw in the control test subjects was induced by an acute, immediate nociceptive response following the formalin injection. This first phase lasted 5 minutes while the second phase started 15-20 minutes after formalin was injected and lasted for 35-40 minutes. A repeated-measures ANOVA was completed and confirmed the presence of a time effect but not a group effect. During the second phase of nociceptive behavior, the research team found that R-phenylpiracetam was able to reduce formalin-induced nociceptive behavior in a dose-dependent manner. The 50 mg/kg dose of R-phenylpiracetam was shown to decrease paw-licking duration by approximately 50%. Administration of S-phenylpiracetam had no effect on the duration of paw-licking in either the first or second phase of nociceptive behavior. [3]

Figure 5: A) Changes in the duration of paw licking in the first phase in response to administration of different treatments. B) Changes in the duration of paw licking in the second phase in response to administration of different treatments.



*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).


[1] Kim S, Park JH, Myung SW, Lho DS. Determination of carphedon in human urine by solid-phase microextraction using capillary gas chromatography with nitrogen-phosphorus detection. Analyst. 1999 Nov;124(11):1559-62. doi: 10.1039/a906027h. PMID: 10746314.

[2] Tiurenkov IN, Bagmetova VV, Shishkina AV, Berestovitskaia VM, Vasil’eva OS, Ostrogliadov ES. [Gender differences in action Fenotropil and its structural analog–compound RGPU-95 on anxiety-depressive behavior animals]. Eksp Klin Farmakol. 2010 Nov;73(11):10-4. Russian. PMID: 21254591.

[3] Zvejniece L, Zvejniece B, Videja M, Stelfa G, Vavers E, Grinberga S, Svalbe B, Dambrova M. Neuroprotective and anti-inflammatory activity of DAT inhibitor R-phenylpiracetam in experimental models of inflammation in male mice. Inflammopharmacology. 2020 Oct;28(5):1283-1292. doi: 10.1007/s10787-020-00705-7. Epub 2020 Apr 11. PMID: 32279140.

RGPU-95 is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.


Gender Differences In The Effects of Phenotropil And Its Structural Analogue



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