Pramiracetam, ≥98%

Chemical Information:

Technical Information:

Background:

Pramiracetam (Diisopropyl-(2-oxopyrrolidin-1-yl)acetamide) is a Nootropic agent belonging to the racetam family of drugs. It is structurally similar to Piracetam and was first synthesized in 1984 as a more potent derivative of the parent compound, Pircetam. Pramiracetam is used in Eastern European countries and has the brand names Remen (Parke-Davis), Neupramir (Lusofarmaco), or Pramistar (Firma).

It is not approved for any use by the US Food and Drug Administration or by the European Medicines Agency. Pramiracetam has been studied as a potential treatment for memory loss associated with Alzheimer's disease and for cognitive problems resulting from brain injury.

Modes of action:                    

Pramiracetam is absorbed well in humans and animals and has a prolonged, yet variable half-life.  In humans, peak plasma concentrations (Cmax) are close to 2.71µg/mL for 400mg oral treatment, around 5.4µg/mL for 800mg, and closer to 8.98µg/mL for a 1600mg administration.[1]

Studies using animals have noted a half-life of around 2.3-3.9 hours and effective absorption in the brain[2], while human studies indicate a longer half-life of between 2 to 8 hours. [3]

Hippocampal cell studies indicate that Pramiracetam is ineffective in inducing changes in hippocampal cells in vitro.[4] Similarly, studies have indicated a failure to significantly influence adrenergic receptors in the serotonergic, dopaminergic, GABAergic, muscarinic, and adenosinic receptors. [5]

Interestingly, studies have shown that adrenalectomy (removal of one or both of the adrenal glands) inhibits the effects of Pramiracetam. This indicates the role of the adrenal glands in Pramiracetam’s mechanism of action.[6]

Furthermore, studies have pointed out that drugs like aminoglutethimide and epoxymexrenone are able to inhibit Pramiracetam’s effects. These drugs are involved in the conversion of cholesterol to pregnenolone and aldosterone inhibition, respectively. These results indicate the role of steroidal hormones in Pramiracetam’s mechanism of action.[7] Additional studies have indicated that raised corticosteroid levels have a limiting effect on the efficacy of racetam drugs, in general. [8]

Further scientific research:

Please note that this is not a comprehensive account of the research to-date on Pramiracetam. For more information, please visit PubMed Central and search the database.  We have included a selection of studies for your consideration.

Clinical reviews:

There is a wide need for more clinical reviews for Pramiracetam and other racetam-like drugs, in general. Meta-analyses and reviews help to assess trends in studies and provide invaluable data analysis with regards to the efficacy of the compounds being studied.

In a 2010 clinical review on Piracetam and Piracetam-like drugs, researchers pointed out that Pramiracetam has a history of efficacy in improving cognitive deficits in patients with traumatic brain injuries. [9]

Human studies:

In a 2007 clinical trial, 65 patients with mild craniocerebral trauma were treated with either Pramiracetam or Piracetam. Data were collected during the first, tenth, and final day of the month-long study. Patients receiving Pramiracetam noted considerable improvement of headaches, dizziness, and nausea, with a better restoration of spatial orientation and feeling than those receiving Piracetam. Furthermore, Pramiracetam appeared to be more effective in restoring memory. [10]

A 1991 study examined the effects of treatment with 400mg Pramiracetam, three times daily, in treating memory and other cognitive problems of males who had suffered brain injuries. The results showed a significant improvement performance in memory, with statistically significant benefits when compared to placebo. The study was a long-term, 18-month trial and included a 1-month review period after the drug was discontinued. [11]

 In 1996, a similar study was conducted on a group of otherwise healthy elderly people. Results showed that those receiving Pramiracetam had statistically significant improvements over those who were doing memory training courses alone. [12]

Animal studies:

A number of animal studies have been conducted using Pramiracetam. Perhaps the best-known study was published in 1986, in which researchers used the radical arm maze task to demonstrate the long-term effects of chronic Pramiracetam treatment. Doses of 7.5 mg/kg and 15 mg/kg were administered daily prior to testing for 7 weeks. Both doses significantly improved performance in reference memory but did not improve working memory. [13]

References:

• [1] Chang T, Young RM, Goulet JR, Yakatan GJ. (1985). Pharmacokinetics of oral pramiracetam in normal volunteers, J Clin Pharmacol, 25(4):291-5.
• [2] Fang Z, Liu X, Xiao Y, Jiang W. (1999). [Pharmacokinetics of pramiracetam in animals]. (Article in Chinese). Hua Xi Yi Ke Da Xue Xue Bao, 30(4):411-3.
• [3] Auteri A, Blardi P, Celasco G, Segre G, Urso R. (1992). Pharmacokinetics of pramiracetam in healthy volunteers after oral administration. Int J Clin Pharmacol Res, 12(3):129-32.
• [4] Xiao P, Staubli U, Kessler M, Lynch G. (1991). Selective effects of aniracetam across receptor types and forms of synaptic facilitation in hippocampus. Hippocampus, 1(4):373-80.
• [5] Pugsley TA, Shih YH, Coughenour L, Steward SF. (1983). Some neurochemical properties of pramiracetam (CI-879), a new cognition-enhancing agent., Drug Development Research, 3(5): 407–420
• [6] Mondadori C, Petschke F. (1987). Do piracetam-like compounds act centrally via peripheral mechanisms? Brain Res, 435(1-2):310-4.
• [7] Mondadori C, Bhatnagar A, Borkowski J, Häusler A. (1990). Involvement of a steroidal component in the mechanism of action of piracetam-like Nootropics, Brain Res, 506(1):101-8.
• [8] Mondadori C, Ducret T, Häusler A. (1992). Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics., Psychopharmacology (Berl), 108(1-2):11-5.
• [9] Malykh AG, Sadaie MR. (2010). Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs, 70(3):287-312.
• [10] Tkachev AV. (2007). [Application of nootropic agents in complex treatment of patients with concussion of the brain]. (Article in Russian). Lik Sprava, (5-6):82-5.
• [11] McLean A, Cardenas DD, Burgess D, Gamzu E. (1991). Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia. Brain Inj, 5(4):375-80.
• [12] De Vreese LP, Neri M, Boiardi R, Ferrari P, Belloi L, Salvioli G. (1996).  Memory training and drug therapy act differently on memory and metamemory functioning: evidence from a pilot study., Arch Gerontol Geriatr, 22 Suppl 1:9-22.
• [13] Murray CL, Fibiger HC. (1986). The effect of pramiracetam (CI-879) on the acquisition of a radial arm maze task, Psychopharmacology (Berl), 89(3):378-81.