PHENYLPIRACETAM 30ML LIQUID (50MG/ML, 1500MG BOTTLE)

$32.99

Phenylpiracetam 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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Description

Phenylpiracetam Liquid

 

 

 

CAS Number 77472-70-9
Other Names Fonturacetam, 4-Phenylpiracetam, Carphedon, Phenotropil, Carphedone, Karfedon, Carphedo, BRN 5030440, UNII-99QW5JU66Y, 99QW5JU66Y, MFCD01456750, PHENOTROPYL
IUPAC Name 2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide
Molecular Formula C₁₂H₁₄N₂O₂
Molecular Weight 218.25
Purity ≥99% Pure (LC-MS)
Liquid Availability 30mL liquid (50mg/mL, 1500mg bottle)
Powder Availability   5 grams
Gel Availability N/A
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 Phenylpiracetam?

Phenylpiracetam, ((R,S)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide, carphendon, phenotropil), is a nootropic compound of the racetam family currently being studied for its potential to combat cognitive degradation, obesity, depression, and fatigue. Phenylpiracetam is a mixture of both an R and S enantiomers with recent findings reporting that R-phenylpiracetam is responsible for the stimulation of locomotion of the compound, while also working with S-phenylpiracetam to inhibit the reuptake of dopamine in the synaptic cleft. Additionally, R-phenylpiracetam has been shown to bind to the norepinephrine transporter (NET), and is generally more active that the S-phenylpiracetam enantiomer [1].

 

Main Research Findings

1) Phenylpiracetam has been found to have a strong antiaggregant effect in models of alloxan-induced diabetes.

2) Selective inhibitors of dopamine, such as S-phenylpiracetam, may have the potential to treat obesity in individuals diagnosed with metabolic syndrome with fewer occurrences of adverse side effects and health consequences.

 

Selected Data

1) Previous research has focused on the ability of nootropic compounds to treat various cognitive disorders due to their ability to activate integral brain functions, as well as stimulate memory, learning, and mental capacity under pathological conditions. That being said, the research team of Zhilyuk et al took into account the role platelet dysfunction plays in cerebrovascular disorders typically treated with nootropics, in order to apply this knowledge to similar vascular disturbances that are seen as a result of long-term progression of diabetes.

For the purpose of this study the experiments were performed using 54 male albino Wistar rats that all weighed between 250-300 grams. All of the test subjects were randomly assigned to 1 of 5 experimental groups including: a passive control group of intact rats, and active control group of rats with alloxan-induced diabetes (ALD), a group of ALD rats administered a of 300 mg/kg dose of pramiracetam, a group of ALD rats administered a 100 mg/kg dose of phenylpiracetam, and a group of ALD rats administered a 500 mg/kg dose of piracetam. The test subjects were induced with experiment diabetes through a subcutaneous injection of a single 150 mg/kg dose of alloxan monohydrate. On day 11 of the study the blood glucose levels of the rats were determined and further experimentation included the rats with hyperglycemia marked by glucose levels greater than 11 mmol/liters [2].

On day 11 after the injection of alloxan, the rats were intragastically administered their assigned experimental compound over the course of 20 days. After 20 days blood samples were collected from each test subject which was then stabilized using 3.8% sodium citrate followed by centrifugation for 15 minutes. The resulting product was platelet-rich plasma the research team was able to effectively assess for the functional activity of the platelets. Using a SOLAR AR 2110 aggregation analyzed, the maximum degree of aggregation was able to be measured and used as a primary indicator of platelet functioning. Also on day 30 a competitive ELISA immunoassay kit was used to measure the concentration of 11-dehydro-TxB in the urine. After the concentration was calculated the results were standardized according to kidney function while the creatinine concentration levels were measured and adjusted using standard protocol [2].

The platelet suspension was used to observe the activity of NO synthase, a compound composed of NOS, NADPH diaphorase. NOS activity in the platelets was quantitatively estimated based on the amount of diformazan present. Additionally, the test samples used by the research were pretreated with paraformaldehyde in order to deactivate all NADPH diaphorase other than NOS [2]. NOS activity was expressed as the amount of diformazen that formed per platelet during a 1 minute period.

2) The research team of Zvejniece et al examined the effects of S-phenylpiracetam on weight gain, levels of glucose and leptin, and overall locomotor activity in an animal experimental model. Weight gain is typically caused by excess energy intake and is characterized by increased adipose tissue that results in a higher risk for comorbidities. Previous research has found that dopaminergic pathways play a crucial role in the control of body weight and food consumption, considering that imaging indicates reduced dopamine receptor availability in obese subjects compared to individuals with a healthy BMI [1].

For the in vivo portion of the study, six male Wistar rats were decapitated in order for the brains to be dissected so the researchers could isolate the striatum. Once isolated, the striatum was homogenized in a sucrose-phosphate buffer, followed by centrifugation for 10 minutes. The resulting supernatant was centrifuged again and the pellet obtained from this final process was resuspended in a sodium-phosphate buffer. The binding assay took place using samples consisting of 60 uL of sodium-phosphate buffer, 20 uL of phenylpiracetam, 20 uL of water, 100 uL of membrane aliquots, and 20 uL of [3H}WIN 35,428. Non-specific binding assays were performed using the same samples with the addition of vanoxerine dihydrochloride and followed by incubation on ice for 2 hours [1]. Finally, in order to measure radioactivity, both free and bound radioligands were separated through the use of rapid filtration achieved by washing of the filters three times with an ice-cold TRIS-HCl buffer. This process allowed for measurement of radioactivity through a liquid scintillation method.

For the in vitro portion of the study sixteen, 6 week old obese male Zucker rats weighing between 130-200 grams were used. These test subjects were compared to eight, age-matched Zucker rats that were leaner weighing from 130-170 grams. The rats were allowed to adapt to their local condition for 7 days prior to the initiation of treatment; the subjects were maintained under standard laboratory conditions with ad libitum access to food and water. The obese Zucker rats were administered a 50 mg/kg dose of S-phenylpiracetam via oral gavage, on a daily basis over a period of 12 weeks. The lean Zucker rats were treated in the same manner, however, instead of S-phenylpiracetam they were administered 50 mg/kg of water [1].

The next in vitro portion of the experiment included 32 male C57BL/6N mice weighing between 21 grams and 25 grams. The mice were allowed to adapt to their local conditions for 7 days prior to the initiation of the experiments; test subjects were maintained under standard laboratory conditions with ad libitum access to food and water. Following the adaptation period the test subjects were randomly assigned to four different treatment groups including: a normal diet, a Western diet, a Western diet with treatment with S-phenylpiracetam, and a Western diet with treatment with R-phenylpiracetam [1]. It is important to mention that the Western diet was characterized as a diet containing 21% fat, 20% protein, and 50% carbohydrates, while the normal diet contained 4.5% fat, 14.5% protein, and 60.1% carbohydrates [1]. The mice receiving active treatment with R- or S-phenylpiracetam were administered 50 mg/kg via oral gavage while the mice on both the Western diet by itself and a normal diet were administered 50 mg/kg of water in the same manner.

The final in vitro experimental group included forty, 16-week old male SW mice weighing from 40-50 grams each. The test subjects were maintained under standard laboratory conditions with ad libitum access to food and water. The mice were randomly assignment to five different groups including: administration of 50 mg/kg of R-phenylpiracetam, administration of 100 mg/kg of R-phenylpiracetam, administration of 50 mg/kg of S-phenylpiracetam, administration of 100 mg/kg of S-phenylpiracetam, and administration of drinking water for the control group [1]. All animals included in the experiment were weighed one time per week in order to make conclusions regarding increases in fat mass by comparing the differences between lean and obese animal mass. The specific formula to calculate fat mass, specifically in the subjects on a Western diet, was as follows: fat mass = average obese animal weight – average lean animal weight. After 12 weeks of treatment and diet manipulation the subjects were placed in individual metabolic cages in order for their food intake to be measured.

Blood glucose tolerance and concentration levels were assessed next. Prior to the glucose tolerance testing the mice and rats were fasted overnight followed by intraperitoneal injection of glucose solution in doses of 1 g/kg for rats and 0.5 g/kg for mice. Blood samples were collected from the tail vein 15, 30, 60, 120, 180, and 240 minutes following administration of the glucose solution. The glucose tolerance test was performed after 8 weeks of treatment for the mice and after 12 weeks of treatment with S-phenylpiracetam for the rats. The same time frames were used when measuring plasma blood glucose concentration, as well as when measuring concentrations of leptin and insulin in the plasma. Glucose concentration values were assessed using a commercially available kit from Instrumentation Laboratory while leptin and insulin was assessed through the use of Mouse Leptin and Rat/Mouse Insulin ELISA kits [1].

Finally, the test subjects underwent an open-field test in order to observe changes in motor activity in the animals following 8 weeks of treatment with S-phenylpiracetam for mice and 12 weeks of treatment for rats. The apparatus used in the test was a square arena where the animals were placed in the center in order for the research team to record the distance moved in cm and the velocity of the movement in cm/seconds, using a video tracking system. The open-field test was performed 60 minutes after administration of the phenylpiracetam enantiomers; the mice were placed in the open field for a 4 minute testing period while the rats were placed in the open field for a 15 minute testing period.

As an additional trial, the research team used the open-field test to examine the motor activity of the rats and mice after a single administration of S- and R-phenylpiracetam, rather than 8-12 weeks of treatment. The test subjects were allowed to explore the apparatus for 10 minutes the day before the experiment followed by return to their original cages. 24 hours after the adaptation period, the experiment took place in two, 12 minute sessions that occurred 30 minutes after the administration of S-phenylpiracetam and 60 minutes after the administration of R-phenylpiracetam. The animals were placed back into the center of the open field so the velocity and the distance traveled could be recorded [1].

 

Discussion

1) The initial results of the study conducted by Zhilyuk et al found that development of ALD in the test subjects was correlated with platelet hyperactivity. The rate of platelet aggregation induced by collagen was found to increase by 35.4% and 24.9% in the experimental groups compared to the test subjects in the passive control group. The rate of platelet aggregation induced by 5 umol/liter ADP was shown to increase by 52.3% and 39.5% in the experimental groups. These findings related to 5 umol/liter ADP-induced aggregation were compared to those of 20 umol/liter of ADP-induced platelet aggregation. The higher concentration was found to increase platelet aggregation by 29.8% and 33.6% [2].

Figure 1: Effects of the nootropics on platelet aggregation induced by 5 umol/liters of ADP.


Figure 2: Effects of the nootropics on platelet aggregation induced by 20 umol/liters of ADP.

When looking specifically at collagen-induced platelet aggregation, administration of phenylpiracetam was found to decrease this parameter by approximately 60%. Similar results were reported when focusing on 5 umol/liter ADP-induced platelet aggregation; phenylpiracetam was found to decrease aggregation by 46.4%. Additionally, in an attempt to define a mechanism of action for the reduction in platelet aggregation, the researchers observed the effects of the nootropic on system production of metabolite 11-dehydro-thromboxane-B. This metabolite was specifically found in urine samples collected from ALD rats and is correlated with an approximately 70% higher aggregation rate than intact animals. After 20 days, treatment with nootropics was shown to reduce the occurrence of 11-dehydro-TxB in urine samples [2].


Figure 3: Effect of the nootropics on platelet aggregation induced by collagen.

To further define the mechanism of antiaggregant activity of phenylpiracetam, NOS activity was observed. NOS function was chosen due to the enzyme’s involvement in the production of NO, an inhibitor of platelet aggregation. The findings of this portion of the study indicated that endothelial dysfunction was related to decreased constitutive NOS activity as a result of platelet aggregation in rats experiencing hyperglycemia. Phenylpiracetam administration was shown to result in a 1.65-fold increase in constitutive NOS activity [2]. In hyperglycemic rats, treatment with phenylpiracetam was also shown to increase the level of NO metabolites in plasma by 41.4% allowing the research team to conclude that the nootropic compounds have the potential to inhibit the aggregation and adhesion of platelets in order to improve blood flow.

2) When looking at the binding assay related to dopamine transportation following treatment with R-phenylpiracetam and S-phenylpiracetam, the results found that both enantiomers of the nootropic competitively bound to the dopamine transport sites, successfully inhibiting the reuptake of dopamine in the synaptic cleft. In addition to the transportation of dopamine, the effects elicited by S-phenylpiracetam on locomotor activity was observed through open-field testing that took place 30 minutes after administration of the nootropic. Treatment with the S enantiomer of phenylpiracetam was shown to increase locomotor activity significantly within the first 4 minutes of the 12 minute trial. From minutes 4-8 and 8-12 locomotion continuously decreased. It is important to note that the 100 mg/kg dose of R-phenylpiracetam was shown to increase locomotor activity to a greater extent than the same dose of S-phenylpiracetam [1].


Figure 4: The recorded locomotor activity levels 30 minutes after administration of either R-phenylpiracetam or S-phenylpiracetam.

When examining the effects of S-phenylpiracetam on weight gain, the researcher utilized two-way ANOVA which revealed a significant correlation between the day of treatment and the experimental group the Zucker rats were included in. The results reported that in comparison to the lean control rats, obese control rats experienced dramatic body weight gain starting at week 2 that persisted until the end of the experiment. The fat mass increase was measured to be 5 grams after the first week of the study; this measurement continued to increase for the remaining experimental time period and was recorded as 173 grams by the end of 12 weeks [1].

In obese rats treated with S-phenylpiracetam, the rate of body weight gain was significantly decreased in comparison to that of the obese control group. This finding was observed starting at the 4th week of the experiment and persisted until the end of the experiment. After 12 weeks of treatment with the nootropic the researchers recorded a 16% decrease in body weight. In terms of food intake, there were no significant differences observed between lean and obese control rats, however, the groups treated with S-phenylpiracetam exhibited a tendency to eat less food in comparison to the obese control rats.


Figure 5: Changes in A) body weight increase, B) fat mass increase, and C) food intake in the lean and obese control groups, as well as the experimental group of obese mice administered S-phenylpiracetam.

Starting from the 2nd week of the experiment, body weight gain was found to be significantly higher in the mice fed with a Western diet rather than the control mice fed a normal diet. As it was previously mentioned, the two-way ANOVA revealed a correlation between day of treatment and experimental group. The related findings of the experiment showed that treatment with R-phenylpiracetam elicited the most significant decrease in body weight during the first two weeks of the study, as well as weeks 6-8. Treatment with S-phenylpiracetam was found to elicit the most significant decrease in body weight starting at week 6 and persisting until the end of the 12 week experimental period [1].

By week 8, the group administered S-phenylpiracetam experienced a 26% decrease in body weight while the average reduction in body weight in the group administered R-phenylpiracetam was 40%. Additionally, there was a significant increase in fat mass in the mice fed a Western diet compared to the mice fed a normal diet. However, the mice treated with S-phenylpiracetam experienced a 45% decreased in fat mass by the 8th week of treatment, while the mice treated with R-phenylpiracetam experience a 69% decrease in fat mass, in comparison to the Western diet-fed control group [1].

Figure 6: Time dependent changes in A) body weight and B) fat mass in mice fed a normal diet, a Western diet, a Western diet with administration of S-phenylpiracetam, and a Western diet with administration of R-phenylpiracetam.

Finally, the research team examined changes in levels of blood glucose, leptin, and insulin in response to treatment with both S- and R-phenylpiracetam. Baseline levels of the obese and lean control rats were similar; the obese control rats experienced an increase in fasted blood glucose concentration beginning 8 weeks after the initiation of the experiment. After 12 weeks, both the fasted and fed obese control rats were experiencing hyperglycemia, however, the subjects treated with S-phenylpiracetam had a significantly lower fed-state blood glucose concentration when compared to the obese control group [1]. It should be mentioned that treatment with the nootropic did not elicit any changes on the blood glucose concentrations in fasted mice. When observing the data gathered from the glucose tolerance test, the researchers were able to conclude the administration of S-phenylpiracetam improved glucose tolerance when compared to the obese control mice.


Figure 7: Changes in A) blood glucose levels and B) glucose tolerance in lean and obese control mice and obese mice treated with S-phenylpiracetam

 

Disclaimer

**LAB USE ONLY**
*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).

 

Citations

[1] Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, Kalvinsh I, Liepinsh E, Dambrova M. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity. Pharmacol Biochem Behav. 2017 Sep;160:21-29. doi: 10.1016/j.pbb.2017.07.009. Epub 2017 Jul 22. PMID: 28743458.

[2] Zhilyuk VI, Levykh AE, Mamchur VI. A study of the mechanisms for antiaggregant activity of pyrrolidone derivatives in rats with chronic hyperglycemia. Bull Exp Biol Med. 2014 Apr;156(6):799-802. doi: 10.1007/s10517-014-2454-8. Epub 2014 May 3. PMID: 24824701.

Phenylpiracetam 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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