|Systematic (IUPAC) name|
|Trade names||Breinox, Dinagen, Lucetam, Nootropil, Nootropyl, Oikamid, Piracetam and many others|
|Routes||Oral, parenteral and vaporized|
|Mol. mass||142.16 g/mol|
|(what is this?)|
Piracetam (sold under many brand names) is a nootropic in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid (pyroglutamate). Piracetam is a cyclic derivative of GABA. Piracetam is prescribed by doctors for some conditions, mainly myoclonus, but is used off-label for a much wider range of applications.
- 1 Effects
- 2 Mechanisms of action
- 3 History
- 4 Approval and usage
- 4.1 Aging
- 4.2 Alcoholism
- 4.3 Alzheimer's and senile dementia
- 4.4 Clotting, coagulation, vasospastic disorders
- 4.5 Depression and anxiety
- 4.6 Stroke, ischemia and symptoms
- 4.7 Developmental coordination disorder and dysgraphia
- 4.8 Schizophrenia
- 4.9 Preventive for breath-holding spells
- 4.10 Closed craniocerebral trauma
- 5 Dosage
- 6 Side effects
- 7 Lucid dreaming
- 8 Availability
- 9 Notes
- 10 See also
- 11 References
- 12 External links
While reviews have been published supporting the use of piracetam in the treatment of a wide range of cognitive disorders, a Cochrane review concluded that there was no such clinical use of piracetam justified based on the published evidence.
Several meta-reviews of literature on piracetam indicate that piracetam increases performance on a variety of cognitive tasks among dyslexic children, though this may reflect its enhancement of cross-hemispheric communication and of cognitive function in general, rather than a specific improvement in whatever causes dyslexia. Piracetam also seems to inhibit brain damage caused by a variety of factors including hypoxia and excessive alcohol consumption.
Piracetam has been studied in an extensive number of clinical experiments, and has shown positive results in the treatment of post-stroke aphasia, epilepsy, cognitive decline following heart and brain surgery, dementia, and myoclonus. Its peripheral vascular effect has indicated its use for vertigo, dyslexia and, at one time, sickle cell anemia as well, but a subsequent Cochrane review of the evidence found that it did not support piracetam's use in sickle cell crisis prevention.
Piracetam possesses pronounced antihypoxic and antiarrhythmic effect; the latter is carried out by decreasing the rhythm rate and increasing the contraction amplitude. The animals treated with piracetam in a dose when its antiarrhythmic effects (300 mg/kg) exhibited a decrease of the membrane potential of erythrocytes as compared with control. Similar effects occurred in the animals treated with lidocaine. It can be concluded that in certain types of arrhythmias the use of piracetam restores the normal rhythm of contractions that is perhaps connected with its positive influence on metabolic processes in the myocardium.
Mechanisms of action
Piracetam's mechanism of action, as with racetams in general, is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as a sedative or stimulant. Piracetam is a positive allosteric modulator of the AMPA receptor. It is hypothesized to act on ion channels or ion carriers; thus leading to increased neuron excitability. GABA brain metabolism and GABA receptors are not affected by piracetam. It has been found to increase blood flow and oxygen consumption in parts of the brain but this may be a side effect of increased brain activity rather than a primary effect or mechanism of action for the drug.
Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors, which are implicated in memory processes. Furthermore, piracetam may have an effect on NMDA glutamate receptors, which are involved with learning and memory processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+). It has been found to increase oxygen consumption in the brain, apparently in connection to ATP metabolism, and increases the activity of adenylate kinase in rat brains. Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5, which is a part of the electron transport mechanism in mitochondria. But in the brain, it also increases the permeability of the mitochondria of some intermediaries of the Krebs cycle.
Piracetam was first synthesized in 1964 by scientists at the Belgian pharmaceutical company UCB led by Dr Corneliu E. Giurgea; struck by its apparent ability to boost mental functioning in even healthy individuals and by its safety, Giurgea coined the term nootropic to describe it and other substances. Piracetam (trade name "Nootropil") was launched clinically by UCB in the early 1970s, and currently is in use in many European countries.
Approval and usage
Piracetam is primarily used in Europe, Asia, South America and the U.S. Piracetam is legal to import into the United Kingdom for personal use with or without prescription, and was unregulated in the United States, as of 2006. However, in August 2010, the FDA issued a single letter to one supplier ordering the discontinuation of the sale of piracetam in the U.S. as a dietary supplement owing to the relatively strict definition of what constitutes a dietary supplement. Under section 201(ff)(1) of the Federal Food Drug and Cosmetic Act, 21 U.S.C. § 321(ff)(1), piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient.Piracetam has no DIN in Canada, and thus cannot be sold but can be imported for personal use in Canada. It has become popular as a cognitive enhancement drug among students. It may even be possibly used for the treatment of childhood autism, a practice partially supported by clinical research.
Alzheimer's and senile dementia
Once thought to be effective for improving cognition in Alzheimer's disease and senile dementia patients, the evidence is now seen as too inconsistent to support the use of piracetam for these conditions.
Clotting, coagulation, vasospastic disorders
Piracetam is useful as a long-term treatment for clotting, coagulation, and vasospastic disorders such as Raynaud's phenomenon and deep-vein thrombosis. It is an extremely safe anti-thrombotic agent that operates through the novel mechanism of inhibiting platelet aggregation and enhancing blood-cell deformability. Because traditional anti-thrombotic drugs operate through the separate mechanism of inhibiting clotting factors, co-administration of piracetam has been shown to highly complement the efficacy and safety of traditional Warfarin/Heparin anti-coagulation therapy. The most effective treatment range for this use is a daily dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart. Piracetam was investigated as a complement or alternative to Warfarin as a safe and effective long-term treatment for recurring deep-vein thrombosis.
Depression and anxiety
Some sources suggest that piracetam's overall effect on lowering depression and anxiety is higher than improving memory. However, depression is reported to be an occasional adverse effect of piracetam.
Stroke, ischemia and symptoms
Developmental coordination disorder and dysgraphia
Due to its supposed effect on nerves and muscles it is sometimes prescribed as an aid to muscle or dexterity training, particularly in cases of agraphia and developmental coordination disorder. There has not been a specific study as to whether it is beneficial in this. Vinpocetine, another purported nootropic with which piracetam is indirectly synergistic, is confirmed to help with these conditions to a certain degree.
At least one study shows that, while piracetam positively affected the cognition of patients suffering from schizophrenia in the same way as it positively affected the cognition of others, the severity of subjects' schizophrenia remained unaffected, for better or worse.
Preventive for breath-holding spells
Two articles support the use of piracetam as a prophylactic for severe cases of breath-holding spells. A 2008 study in the International Journal of Psychiatry Medicine supported the notion that piracetam was effective as a preventive, but did not use a control to evaluate results against normal recovery times from severe BHS. A 1998 study by the Turkish ministry of health evaluated 76 children, half of them in a control group. Children in the experimental group were three times as, and almost completely likely, to exhibit "overall control" over their BHS, with BHS episodes dropping by 60% over two months.
The 2008 study notes:
Breath holding spells (BHS) are apparently frightening events occurring in otherwise healthy children. Generally, no medical treatment is recommended and parental reassurance is believed to be enough, however, severe BHS can be very stressful for the parents and a pharmacological agent may be desired in some of these children.
Closed craniocerebral trauma
Piracetam has positive therapeutic effects on adolescents with closed craniocerebral trauma (CCT). Treatment with piracetam was initiated 1.5 to 5 years after trauma. Compared to controls, after one month of daily treatment with 1600–2400 mg of piracetam there were meaningful and statistically significant improvements in the higher mental functions (visual memory, attention and executive), motor functions (gait, balance and sequential limb movements) and in the rates of cognitive and motor operations.
For blood coagulation, clotting, and vasospastic disorders such as Raynaud's phenomenon or deep-vein thrombosis, the most effective treatment range is a daily oral dose of 4.8 to 9.6 grams divided into three daily doses at 8 hours apart. The LD-50 for oral consumption in humans has not been determined, however the LD-50 for mice is 5.6g/kg for rats, and 20g/kg for mice, indicating extremely low toxicity.
Piracetam has been found to have very few side effects, and those it has are typically "few, mild, and transient." A large-scale, 12-week trial of high-dose piracetam found no adverse effects occurred in the group taking piracetam as compared to the placebo group. Many other studies have likewise found piracetam to be well tolerated.
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, tremor, and hyperkinesia, are occasionally reported. Other reported side effects include somnolence, weight gain, clinical depression, weakness, increased libido, and hypersexuality.
|This section does not cite any references or sources. (June 2013)|
||This section possibly contains original research. (June 2013)|
Piracetam has become a popular supplement in the subculture of lucid dreaming. Its use has been largely made popular by a book published by Thomas Yuschak titled Advanced Lucid Dreaming: The Power of Supplements. Piracetam is not used directly to cause vivid dreams; it is even said to prevent them. The premise for its use is to counter the desensitization of acetylcholine receptors in the brain caused by taking another supplement, galantamine, which is said to cause stronger, more vivid dreaming experiences. Piracetam is taken immediately after having a lucid dream experience with galantamine. The lucid dreamer will then not take the supplement combination again until the galantamine has completely left their system (approximately 30 hours). Piracetam has a peak plasma time of 1.5 hours and an elimination half-life equal to 5 hours. For the purpose of lucid dreaming dosing is much lower than doses taken in clinical studies, averaging typically 2400 mg.
Piracetam is sold under a wide variety of brand names world wide. Popular trade names for piracetam in Europe are Nootropil and Lucetam, among many others. In Argentina, it is made by GlaxoSmithKline S.A. laboratories and sold under the trade name of Noostan (800 mg or 1200 mg). In Venezuela and Ecuador, piracetam is produced by Laboratorios Farma S.A. and sold under the brand name Breinox. In Mexico is produced by UCB de Mexico, and sold under the brand name of Nootropil. Other names include Nootropil in The United States, Europe, Brazil, Hong Kong, India, and Mexico; Lucetam, Oikamid, Smart, Geratam, and Biotropil in Europe and Brazil; Neurobasal in Colombia; Breinox in Ecuador and Venezuela; Noostan in Argentina; Stimulan in Egypt; and Nocetan in Latin America.
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|Wikimedia Commons has media related to Piracetam.|
- Brivaracetam—another analogue of Piracetam with the same additional side chain as Levetiracetam and a three carbon chain. It exhibits greater antiepileptic properties than Levetiracetam but with a somewhat smaller, although still high, therapeutic range. As of 2011, it is in 3rd stage pharmaceutical trials
- Levetiracetam—an analogue of Piracetam bearing an additional CH3-CH2- sidechain and bearing antiepileptic pharmacological properties through a poorly understood mechanism probably related to its affinity for the vesicle protein SV2A
- UCB Pharma Limited (2005). "Nootropil 800 mg & 1200 mg Tablets and Solution". electronic Medicines Compendium. Datapharm Communications. Retrieved 8 December 2005.
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- U.S. National Library of Medicine