Piracetam
- ATC:N06BX03
- MW:142.16 g/mol
- CAS-RN:7491-74-9
- InChI Key:GMZVRMREEHBGGF-UHFFFAOYSA-N
- InChI:InChI=1S/C6H10N2O2/c7-5(9)4-8-3-1-2-6(8)10/h1-4H2,(H2,7,9)
- EINECS:231-312-7
- LD50:9200 mg/kg (M, i.v.); 2 g/kg (M, p.o.)
Piracetam is in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It is a derivative of the neurotransmitter GABA[5] and shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Piracetam is a cyclic derivative of GABA (gamma-aminobutyric acid). Related drugs include the anticonvulsants levetiracetam and brivaracetam, and the putative nootropics aniracetam and phenylpiracetam.Piracetam is a drug marketed as a treatment for myoclonus[3] and a cognitive enhancer.[4] Evidence to support its use is unclear, with some studies showing modest benefits in specific populations and others showing minimal or no benefit.[5][6] Piracetam is sold as a medication in many European countries. Sale of piracetam is not illegal in the United States, although it is not regulated nor approved by the FDA so it must be marketed as a dietary supplement.[4]
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Efficacy
Dementia
A 2001 Cochrane review concluded that there was not enough evidence to support piracetam for dementia or cognitive problems.[6] A 2005 review found some evidence of benefit in older subjects with cognitive impairment.[5] In 2008, a working group of the British Academy of Medical Sciences noted that many of the trials of piracetam for dementia were flawed.[7]
There is no good evidence that piracetam is of benefit in treating vascular dementia.[8]
Depression and anxiety
Some sources suggest that piracetam’s overall effect on lowering depression and anxiety is higher than on improving memory.[9] However, depression is reported to be an occasional adverse effect of piracetam.[10]
Other
Piracetam may facilitate the deformability of erythrocytes in capillary which is useful for cardiovascular disease.[5][3]
Peripheral vascular effects of piracetam have suggested its use potential for vertigo, dyslexia, Raynaud’s phenomenon and sickle cell anemia.[5][3] There is no evidence to support piracetam’s use in sickle cell crisis prevention[11] or for fetal distress during childbirth.[12] There is no evidence for benefit of piracetam with acute ischemic stroke,[13] though there is debate as to its utility during stroke rehabilitation.[14][15]
Anti-vasospasm
Piracetam has been found to diminish erythrocyte adhesion to vascular wall endothelium, making any vasospasm in the capillary less severe. This contributes to its efficacy in promoting microcirculation, including to the brain and kidneys.[5][3]
Side effects
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, tremor, and hyperkinesia, are occasionally reported.[10][16][17] Other reported side effects include somnolence, weight gain, clinical depression, weakness, increased libido, and hypersexuality.[10]
According to a 2005 review, piracetam has been observed to have the following side effects: hyperkinesia, weight gain, nervousness, somnolence, depression and asthenia.[5]
Piracetam reduces platelet aggregation as well as fibrinogen concentration, and thus is contraindicated to patients suffering from cerebral hemorrhage.[5][3]
Toxicity
Piracetam does not appear to be acutely toxic at the doses used in human studies.[6][18][19]
The LD50 for oral consumption in humans has not been determined.[20] The LD50 is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely low acute toxicity.[21] For comparison, in rats the LD50 of vitamin C is 12 g/kg and the LD50 of table salt is 3 g/kg.
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.[5] Piracetam is a positive allosteric modulator of the AMPA receptor, although this action is very weak and its clinical effects may not necessarily be mediated by this action.[22] It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability.[20] GABA brain metabolism and GABA receptors are not affected by piracetam[23]
Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors[citation needed], which are implicated in memory processes.[24] 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.[24][25] Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na+, K+).[20] 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.[26][27] Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5,[28] which is a part of the electron transport mechanism in mitochondria. But in the brain, it also increases the permeability of some intermediates of the Krebs cycle through the mitochondrial outer membrane.[26]
Piracetam inhibits N-type calcium channels. The concentration of piracetam achieved in central nervous system after a typical dose of 1200 mg (about 100 μM)[29] is much higher than the concentration necessary to inhibit N-type calcium channels (IC50 of piracetam in rat neurons was 3 μM).[30]
History
Piracetam was first made some time between the 1950s and 1964 by Corneliu E. Giurgea.[31] There are reports of it being used for epilepsy in the 1950s.[32]
Society and culture
In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students.[33]
Legal status
Piracetam is an uncontrolled substance in the United States meaning it is legal to possess without a license or prescription.[34]
Regulatory status
In the United States, piracetam is not approved by the Food and Drug Administration.[1] Piracetam is not permitted in compounded drugs or dietary supplements in the United States.[35] Nevertheless, it is available in a number of dietary supplements.[4]
In the United Kingdom, piracetam is approved as a prescription drug Prescription Only Medicine (POM) number is PL 20636/2524[36] for adult with myoclonus of cortical origin, irrespective of cause, and should be used in combination with other anti-myoclonic therapies.[37]
In Japan piracetam is approved as a prescription drug.[38]
Piracetam has no DIN in Canada, and thus cannot be sold but can be imported for personal use in Canada.[39]
In Hungary, piracetam was a prescription-only medication, but as of 2020, no prescription is required and piracetam is available as an over-the-counter drug under the name Memoril Mite, and is available in 600 mg pills.
SYN
SYN
http://www.cjph.com.cn/EN/abstract/abstract373.shtml
With absolute ethanol as the solvent, ethyl 4-chloro-n-butanoate and glycinamide hydrochloride were refluxed for 20 h in the presence of sodium bicarbonate to obtain central stimulant piracetam. After recrystallization from isopropanol, the yield was about 58% with a purity of 99.6%.
SYN
CAS-RN | Formula | Chemical Name | CAS Index Name |
---|---|---|---|
79-07-2 | C2H4ClNO | 2-chloroacetamide | Acetamide, 2-chloro- |
105-39-5 | C4H7ClO2 | ethyl chloroacetate | Acetic acid, chloro-, ethyl ester |
61516-73-2 | C8H13NO3 | ethyl 2-oxo-1-pyrrolidineacetate | 1-Pyrrolidineacetic acid, 2-oxo-, ethyl ester |
616-45-5 | C4H7NO | 2-pyrrolidone | 2-Pyrrolidinone |
PATENT
https://patents.google.com/patent/CN104478779A/zh
References
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- ^ Leaflet of Piracetam.
- ^ Jump up to:a b c d e “Nootropil Tablets 1200 mg”. (emc). 15 February 2017. Retrieved 14 April 2019.
- ^ Jump up to:a b c Cohen, Pieter A.; Zakharevich, Igor; Gerona, Roy (25 November 2019). “Presence of Piracetam in Cognitive Enhancement Dietary Supplements”. JAMA Internal Medicine. 180 (3): 458–459. doi:10.1001/jamainternmed.2019.5507. PMC 6902196. PMID 31764936.
- ^ Jump up to:a b c d e f g h i 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. PMC 6741724. PMID 16007238.
- ^ Jump up to:a b c 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.
- ^ Horne G, et al. (May 2008). Brain science, addiction and drugs(PDF) (Report). Academy of Medical Sciences. p. 145. ISBN 978-1-903401-18-7.
- ^ Farooq MU, Min J, Goshgarian C, Gorelick PB (September 2017). “Pharmacotherapy for Vascular Cognitive Impairment”. CNS Drugs(Review). 31 (9): 759–776. doi:10.1007/s40263-017-0459-3. PMID 28786085. S2CID 23271739.
Other medications have been considered or tried for the treatment of VCI or VaD. These include […] piracetam. There is no convincing evidence about the efficacy of these medications in the treatment of VCI.
- ^ 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. S2CID 12176745.
- ^ Jump up to:a b c Nootropil®. Arzneimittel-Kompendium der Schweiz. 2013-09-12. Retrieved 2013-10-27.
- ^ Al Hajeri A, Fedorowicz Z (February 2016). “Piracetam for reducing the incidence of painful sickle cell disease crises”. The Cochrane Database of Systematic Reviews. 2: CD006111. doi:10.1002/14651858.CD006111.pub3. PMC 7390168. PMID 26869149.
- ^ Hofmeyr, GJ; Kulier, R (13 June 2012). “Piracetam for fetal distress in labour”. The Cochrane Database of Systematic Reviews (6): CD001064. doi:10.1002/14651858.CD001064.pub2. PMC 7048034. PMID 22696322.
- ^ Ricci S, Celani MG, Cantisani TA, Righetti E (September 2012). “Piracetam for acute ischaemic stroke”. The Cochrane Database of Systematic Reviews (9): CD000419. doi:10.1002/14651858.CD000419.pub3. PMC 7034527. PMID 22972044.
- ^ Zhang J, Wei R, Chen Z, Luo B (July 2016). “Piracetam for Aphasia in Post-stroke Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials”. CNS Drugs. 30 (7): 575–87. doi:10.1007/s40263-016-0348-1. PMID 27236454. S2CID 22955205.
- ^ Yeo SH, Lim ZI, Mao J, Yau WP (October 2017). “Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials”. Clinical Drug Investigation. 37 (10): 901–928. doi:10.1007/s40261-017-0558-4. PMID 28756557. S2CID 6520934.
- ^ 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): 100–106. doi:10.1007/BF00429000. PMID 6415738. S2CID 32702769.
- ^ Hakkarainen H, Hakamies L (1978). “Piracetam in the treatment of post-concussional syndrome. A double-blind study”. European Neurology. 17 (1): 50–55. doi:10.1159/000114922. PMID 342247.
- ^ Koskiniemi M, Van Vleymen B, Hakamies L, Lamusuo S, Taalas J (March 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): 344–348. doi:10.1136/jnnp.64.3.344. PMC 2169975. PMID 9527146.
- ^ Fedi M, Reutens D, Dubeau F, Andermann E, D’Agostino D, Andermann F (May 2001). “Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy”. Archives of Neurology. 58 (5): 781–786. doi:10.1001/archneur.58.5.781. PMID 11346373.
- ^ Jump up to:a b c Gouliaev AH, Senning A (May 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. S2CID 18122566.
- ^ “Piracetam Material Safety Sheet” (PDF). Spectrum.
- ^ Ahmed AH, Oswald RE (March 2010). “Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors”. Journal of Medicinal Chemistry. 53 (5): 2197–203. doi:10.1021/jm901905j. PMC 2872987. PMID 20163115.
- ^ Giurgea CE (January 1982). “The nootropic concept and its prospective implications”. Drug Development Research. 2 (5): 441–446. doi:10.1002/ddr.430020505. ISSN 1098-2299. S2CID 145059666.
- ^ Jump up to:a b 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 (March 1999). “Piracetam: novelty in a unique mode of action”. Pharmacopsychiatry. 32 (Suppl 1): 2–9. doi:10.1055/s-2007-979230. PMID 10338102.
- ^ Jump up to:a b 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 (October 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.
- ^ Yeh HH, Yang YH, Ko JY, Chen SH (July 2006). “Rapid determination of piracetam in human plasma and cerebrospinal fluid by micellar electrokinetic chromatography with sample direct injection”. J Chromatogr A. 1120 (1–2): 27–34. doi:10.1016/j.chroma.2005.11.071. PMID 16343512.
- ^ Bravo-Martínez J, Arenas I, Vivas O, Rebolledo-Antúnez S, Vázquez-García M, Larrazolo A, García DE (October 2012). “A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons”. Exp Biol Med (Maywood). 237 (10): 1209–18. doi:10.1258/ebm.2012.012128. PMID 23045722.
- ^ Li JJ, Corey EJ (2013). Drug Discovery: Practices, Processes, and Perspectives. John Wiley & Sons. p. 276. ISBN 9781118354469.
- ^ Schmidt D, Shorvon S (2016). The End of Epilepsy?: A History of the Modern Era of Epilepsy Research 1860-2010. Oxford University Press. p. 69. ISBN 9780198725909.
- ^ Medew J (1 October 2009). “Call for testing on ‘smart drugs‘“. Fairfax Media. Retrieved 29 May 2014.
- ^ “Erowid Piracetam Vault: Legal Status”.
- ^ Jann Bellamy (26 September 2019). “FDA proposes ban on curcumin and other naturopathic favorites in compounded drugs”. Science-Based Medicine.
- ^http://www.mhra.gov.uk/home/groups/spcpil/documents/spcpil/con1547788739542.pdf
- ^ “Nootropil Tablets 800 mg”. (emc).
- ^ “UCB’s piracetam approved in Japan”. The Pharma Letter. 25 November 1999.
- ^ “Guidance Document on the Import Requirements for Health Products under the Food and Drugs Act and its Regulations (GUI-0084)”. Health Canada / Health Products and Food Branch Inspectorate. 1 June 2010. Retrieved 15 December 2019.
- UCB Pharma Limited (2005). “Nootropil 800 mg & 1200 mg Tablets and Solution”. electronic Medicines Compendium. Datapharm Communications. Archived from the original on 7 December 2006. Retrieved 8 December 2005.
External links
Gouliaev AH, Senning A (May 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. S2CID 18122566.
Clinical data | |
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Trade names | Breinox, Dinagen, Lucetam, Nootropil, Nootropyl, Oikamid, Piracetam and many others |
AHFS/Drugs.com | International Drug Names |
Routes of administration |
By mouth, parenteral, or vaporized |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | ~100% |
Onset of action | Swiftly following administration. Food delays time to peak concentration by 1.5 h approximately to 2–3 h since dosing.[2] |
Elimination half-life | 4–5 h |
Excretion | Urinary |
Identifiers | |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.028.466 |
Chemical and physical data | |
Formula | C6H10N2O2 |
Molar mass | 142.158 g·mol−1 |
3D model (JSmol) | |
Melting point | 152 °C (306 °F) |
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///////////UCB 6215, Nootropic, PIRACETAM