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|Systematic (IUPAC) name|
|Trade names||Breinox, Dinagen, Lucetam, Nootropil, Nootropyl, Oikamid, Piracetam and many others|
|Oral, parenteral, or vaporized|
|(what is this?)|
Piracetam (sold under many brand names) is a nootropic drug in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Piracetam is a cyclic derivative of GABA. In the United States, it is not approved by the US Food and Drug Administration for any medical use and it is not permitted to be sold as a dietary supplement. In the UK, piracetam is prescribed mainly for myoclonus, but is used off-label for other conditions. Evidence to support its use for many conditions is unclear.
- 1 Medical uses
- 2 Side effects
- 3 Mechanisms of action
- 4 History
- 5 Approval and usage
- 6 Availability
- 7 See also
- 8 Notes
- 9 References
- 10 External links
A 2001 Cochrane review concluded that there was not enough evidence to support piracetam for dementia or cognitive problems. A 2002 review and 2005 review concluded that piracetam had some positive effects in older patients with these problems. In 2008, a working group of the British Academy of Medical Sciences noted that many of the trials of piracetam for dementia were flawed.
Peripheral vascular effects of piracetam have suggested its use potential for vertigo, dyslexia and sickle cell anemia. A subsequent Cochrane review of the evidence did not support piracetam's use in sickle cell crisis prevention. Piracetam may have potential for the treatment of the symptoms of childhood autism.[non-primary source needed]
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.
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 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. It was also used by Janz in the 1950's for Juvenile Myoclonic Epilepsy. 
Approval and usage
Piracetam is primarily used in Europe, Asia, and South America. In the United States, it is not approved by the US Food and Drug Administration for any medical use and it is not permitted to be sold as a dietary supplement. Piracetam is legal to import into the United Kingdom for personal use with or without prescription. 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.
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 on improving memory. However, depression is reported to be an occasional adverse effect of piracetam.
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.
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.
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;Stimulan in Egypt; and Nocetan in Latin America.
|Wikimedia Commons has media related to Piracetam.|
- Brivaracetam—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
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- "Nootropil". NetDoctor.co.uk. 8 July 2004. Retrieved 21 September 2009.
- Flicker, L; Grimley Evans, G (2001). "Piracetam for dementia or cognitive impairment.". The Cochrane database of systematic reviews (2): CD001011. doi:10.1002/14651858.CD001011. PMID 11405971.
- Waegemans, T; Wilsher, CR; Danniau, A; Ferris, SH; Kurz, A; Winblad, B (2002). "Clinical efficacy of piracetam in cognitive impairment: a meta-analysis.". Dementia and geriatric cognitive disorders 13 (4): 217–24. doi:10.1159/000057700. PMID 12006732.
- Winblad, B (2005). "Piracetam: a review of pharmacological properties and clinical uses". CNS Drug Reviews 11 (2): 169–82. doi:10.1111/j.1527-3458.2005.tb00268.x. PMID 16007238.
- Horne G et al. (May 2008). Brain science, addiction and drugs (PDF) (Report). Academy of Medical Sciences. p. 145. ISBN 1-903401-18-6.
- Talbot, Margaret (27 April 2009). "Brain Gain: The underground world of 'neuroenhancing' drugs". The New Yorker. Retrieved 21 September 2009.
- Al Hajeri, AA; Fedorowicz, Z; Omran, A; Tadmouri, GO (18 April 2007). "Piracetam for reducing the incidence of painful sickle cell disease crises.". The Cochrane database of systematic reviews (2): CD006111. doi:10.1002/14651858.CD006111.pub2. PMID 17443614.
- Akhondzadeh, S., et al. A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder. Child Psychiatry and Human Development, Vol 39(3), Sep, 2008. pp. 237–245.
- Koskiniemi, M; Van Vleymen, B; Hakamies, L; Lamusuo, S; Taalas, J (1998). "Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo". Journal of neurology, neurosurgery, and psychiatry 64 (3): 344–8. doi:10.1136/jnnp.64.3.344. PMC 2169975. PMID 9527146.
- De Reuck, J; Van Vleymen, B (1999). "The clinical safety of high-dose piracetam--its use in the treatment of acute stroke". Pharmacopsychiatry. 32 Suppl 1: 33–7. doi:10.1055/s-2007-979234. PMID 10338106.
- Fedi, M; Reutens, D; Dubeau, F; Andermann, E; D'agostino, D; Andermann, F (2001). "Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy". Archives of neurology 58 (5): 781–6. doi:10.1001/archneur.58.5.781. PMID 11346373.
- Giurgea, C.; Salama, M. (1977). "Nootropic drugs". Prog Neuro-Psychopharmacolgy 1 (3–4): 235–247. doi:10.1016/0364-7722(77)90046-7.
- Nootropil®. Arzneimittel-Kompendium der Schweiz. 2013-09-12. Retrieved 2013-10-27.
- Chouinard, G; Annable, L; Ross-Chouinard, A; Olivier, M; Fontaine, F (1983). "Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment". Psychopharmacology 81 (2): 100–6. doi:10.1007/BF00429000. PMID 6415738.
- Hakkarainen, H; Hakamies, L (1978). "Piracetam in the treatment of post-concussional syndrome. A double-blind study". European neurology 17 (1): 50–5. doi:10.1159/000114922. PMID 342247.
- Gouliaev, AH; Senning, A (1994). "Piracetam and other structurally related nootropics". Brain research. Brain research reviews 19 (2): 180–222. doi:10.1016/0165-0173(94)90011-6. PMID 8061686.
- "Piracetam Material Safety Sheet" (PDF). Spectrum.
- Ahmed, A; Oswald, R (2010). "Piracetam Defines a New Binding Site for Allosteric Modulators of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors". Journal of Medicinal Chemistry 53 (5): 2197–2203. doi:10.1021/jm901905j. PMC 2872987. PMID 20163115.
- Jordaan, B; Oliver, DW; Dormehl, IC; Hugo, N (1996). "Cerebral blood flow effects of piracetam, pentifylline, and nicotinic acid in the baboon model compared with the known effect of acetazolamide". Arzneimittel-Forschung 46 (9): 844–7. PMID 8876930.
- Winnicka, K; Tomasiak, M; Bielawska, A (2005). "Piracetam--an old drug with novel properties?". Acta poloniae pharmaceutica 62 (5): 405–9. PMID 16459490.
- Müller, WE; Eckert, GP; Eckert, A (1999). "Piracetam: novelty in a unique mode of action". Pharmacopsychiatry. 32 Suppl 1: 2–9. doi:10.1055/s-2007-979230. PMID 10338102.
- Grau, M; Montero, JL; Balasch, J (1987). "Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat". General pharmacology 18 (2): 205–11. doi:10.1016/0306-3623(87)90252-7. PMID 3569848.
- Nickolson, VJ; Wolthuis, OL (1976). "Effect of the acquisition-enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine". Biochemical pharmacology 25 (20): 2241–4. doi:10.1016/0006-2952(76)90004-6. PMID 985556.
- Tacconi, MT; Wurtman, RJ (1986). "Piracetam: physiological disposition and mechanism of action". Advances in neurology 43: 675–85. PMID 3946121.
- S. D. Shorvon (2004). "Piracetam". In Simon D. Shorvon, David Fish, Emilio Perucca, W E Dodson. The treatment of epilepsy. Wiley–Blackwell. pp. 489–495. ISBN 978-0-632-06046-7.
- Medew, Julia (October 1, 2009). "Call for testing on 'smart drugs'". Fairfax Media. Retrieved 29 May 2014.
- Moriau, M; Lavenne-Pardonge, E; Crasborn, L; Von Frenckell, R; Col-Debeys, C (1993). "Treatment of the Raynaud's phenomenon with piracetam". Arzneimittel-Forschung 43 (5): 526–35. PMID 8328997.
- Moriau, M; Crasborn, L; Lavenne-Pardonge, E; Von Frenckell, R; Col-Debeys, C (1993). "Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects". Arzneimittel-Forschung 43 (2): 110–8. PMID 8457235.
- Moriau, M; Lavenne-Pardonge, E; Crasborn, L; Von Frenckell, R; Col-Debeys, C (1995). "The treatment of severe or recurrent deep venous thrombosis. Beneficial effect of the co-administration of antiplatelet agents with or without rheological effects, and anticoagulants". Thrombosis research 78 (6): 469–82. doi:10.1016/0049-3848(95)00081-2. PMID 15714749.
- Malykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767.
- Azam M, Bhatti N, Shahab N (2008). "Piracetam in severe breath holding spells". Int J Psychiatry Med 38 (2): 195–201. doi:10.2190/PM.38.2.f. PMID 18724570.
- Donma MM (January 1998). "Clinical efficacy of piracetam in treatment of breath-holding spells". Pediatr. Neurol. 18 (1): 41–5. doi:10.1016/S0887-8994(97)00153-7. PMID 9492090.
- Zavadenko, NN; Guzilova, LS (2009). "Sequelae of closed craniocerebral trauma and the efficacy of piracetam in its treatment in adolescents". Neuroscience and Behavioral Physiology 39 (4): 323–8. doi:10.1007/s11055-009-9146-2. PMID 19340573.
- 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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- "Improved mitochondrial function in brain aging and Alzheimer disease – the new mechanism of action of the old metabolic enhancer piracetam" (Leuner et al. 2010)
- U.S. National Library of Medicine