Wikipedia

Piracetam

Piracetamis adrugthat has efficacy incognitive disorders,vertigo,corticalmyoclonus,dyslexia,andsickle cell anemia;sources differ on its usefulness fordementia.[3][4][5]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 theFDA,so it is legally sold for research use only.[6]

Piracetam
Clinical data
Trade namesBreinox, Dinagen, Lucetam, Nootropil, Nootropyl, Oikamid, Piracetam, others
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth,parenteral,inhalation
ATC code
Legal status
Legal status
  • AU:S4(Prescription only)
  • CA:Unscheduled
  • UK:POM(Prescription only)
  • US:Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use indietary supplements,food,ormedicineis unlawful; otherwise uncontrolled.[1])
Pharmacokineticdata
Bioavailability~100%
Onset of actionSwiftly following administration. Food delays time to peak concentration by 1.5happroximately to 2–3 h since dosing.[2]
Eliminationhalf-life4–5 hours
ExcretionUrinary
Identifiers
  • 2-(2-Oxopyrrolidin-1-yl)acetamide
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.028.466Edit this at Wikidata
Chemical and physical data
FormulaC6H10N2O2
Molar mass142.158g·mol−1
3D model (JSmol)
Melting point152 °C (306 °F)
  • O=C1N(CC(=O)N)CCC1
  • InChI=1S/C6H10N2O2/c7-5(9)4-8-3-1-2-6(8)10/h1-4H2,(H2,7,9)checkY
  • Key:GMZVRMREEHBGGF-UHFFFAOYSA-NcheckY
(verify)

Piracetam is in theracetamsgroup, with chemical name2-oxo-1-pyrrolidine acetamide.It is a cyclic derivative of the neurotransmitterGABA[4]and shares the same 2-oxo-pyrrolidone base structure withpyroglutamic acid.Related drugs include the anticonvulsantslevetiracetamandbrivaracetam,and the putative nootropicsaniracetamandphenylpiracetam.

Efficacy

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Dementia

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A 2001Cochrane reviewconcluded that there was not enough evidence to support piracetam fordementiaor cognitive problems.[5]A 2005 review found some evidence of benefit in older subjects with cognitive impairment.[4]In 2008, a working group of the BritishAcademy of Medical Sciencesnoted that many of the trials of piracetam for dementia were flawed.[7]

There is insufficient evidence of piracetam as a treatment forvascular dementia.[8]

Depression and anxiety

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Some sources suggest that piracetam's overall effect on loweringdepressionandanxietyis higher than on improving memory.[9]However, depression is reported to be an occasional adverse effect of piracetam.[10]

Attention deficit hyperactivity disorder (ADHD)

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Several clinical trials have looked at piracetam's efficacy as a treatment forADHD.Many of these have found that the drug fails to deliver the same therapeutic effects as current standard treatments for the disorder.[11][unreliable source?]However, more than one study has found piracetam to be highly synergistic with standard ADHD therapies, accelerating and potentiating their therapeutic effects. One 2008 clinical trial found that the combination of piracetam andatomoxetinewas more effective than atomoxetine alone.[12]

While piracetam may be an effective adjuvant therapy for ADHD (when used with specific medications), there is no evidence that it is effective when used in isolation.

Other

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Piracetam may facilitate thedeformability of erythrocytesincapillarywhich is useful for cardiovascular disease.[4][3]

Peripheral vascular effects of piracetam have suggested its use potential forvertigo,dyslexia,Raynaud's phenomenonandsickle cell anemia.[4][3]There is no evidence to support piracetam's use in sickle cell crisis prevention[13]or forfetal distressduring childbirth.[14]There is no evidence for benefit of piracetam withacuteischemic stroke,[15]though there is debate as to its utility during stroke rehabilitation.[16][17]

Anti-vasospasm

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Piracetam has been found to diminisherythrocyteadhesionto vascular wallendothelium,making anyvasospasmin thecapillaryless severe. This contributes to its efficacy in promotingmicrocirculation,including to the brain and kidneys.[4][3]

Side effects

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Symptoms includinganxiety,insomnia,irritability,headache,agitation,tremor,andhyperkinesiaare occasionally reported.[10][18][19]Other reported side effects includesomnolence,weight gain,clinical depression,weakness,increasedlibido,andhypersexuality.[10]

According to a 2005 review, piracetam has been observed to have the following side effects: hyperkinesia,weight gain,anxiety, somnolence, depression, and weakness.[4]

Piracetam reducesplatelet aggregationas well asfibrinogenconcentration, and thus is contraindicated to patients with cerebral hemorrhage.[4][3]

Toxicity

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TheLD50for oral consumption in humans has not been determined.[20]The LD50is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely lowacute toxicity.[21]For comparison, in rats the LD50ofvitamin Cis 12 g/kg and the LD50of table salt is 3 g/kg.

Mechanisms of action

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Piracetam'smechanism of action,as withracetamsin general, is not fully understood. The drug influences neuronal and vascular functions and influences cognitive function without acting as asedativeorstimulant.[4]Piracetam is apositive allosteric modulatorof theAMPA 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]GABAbrain metabolism andGABA receptorsare not affected by piracetam[23]

Piracetam increases the action of theneurotransmitteracetylcholineviamuscariniccholinergic(ACh)receptors[citation needed],which are implicated inmemoryprocesses.[24]Furthermore, piracetam may have an effect onNMDAglutamatereceptors, which are involved withlearningandmemoryprocesses. Piracetam is thought to increase cell membrane permeability.[24][25]Piracetam may exert its global effect on brain neurotransmission via modulation ofion channels(i.e.,Na+,K+).[20]It has been found to increase oxygen consumption in the brain, apparently in connection toATPmetabolism, and increases the activity ofadenylate kinasein rat brains.[26][27]Piracetam, while in the brain, appears to increase the synthesis ofcytochrome b5,[28]which is a part of theelectron transportmechanism inmitochondria.But in the brain, it also increases the permeability of some intermediates of theKrebs cyclethrough the mitochondrial outer membrane.[26]

Piracetam inhibitsN-type calcium channels.The concentration of piracetam achieved incentral nervous systemafter a typical dose of 1200 mg (about 100 μM)[29]is much higher than the concentration necessary to inhibitN-type calcium channels(IC50of piracetam in rat neurons was 3 μM).[30]

History

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Piracetam was first made some time between the 1950s and 1964 byCorneliu E. Giurgea.[31]There are reports of it being used for epilepsy in the 1950s.[32]

Society and culture

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In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students.[33]

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Piracetam is an uncontrolled substance in the United States, meaning it is legal to possess without a license or prescription.[34]Use of piracetam in food, supplements, medical devices, insecticides, infant formula, cosmetics, animal feed, animal drugs, tobacco products, and drugs is unlawful and constitutes an act of misbranding.

Regulatory status

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In the United States, piracetam is not approved by theFood and Drug Administration.[1]Piracetam is not permitted in compounded drugs or dietary supplements in theUnited States.[35]Like most research chemicals, it has been available over-the-counter, self-regulated, and third-party lab tested by many U.S. companies for decades.[6]Nonetheless it is still, for the purposes of U.S. law, a "New Drug" as defined by 21 U.S. Code § 321(p)(1).

In the United Kingdom, piracetam is approved as a prescription drug[36]for adults withmyoclonusof 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]

In the Czech Republic, piracetam is available without prescription.[39][40]

Piracetam has noDINin Canada, and thus cannot be sold, but can be imported for personal use in Canada.[41]

In Hungary, piracetam was a prescription-only medication, but as of 2020, no prescription is required and piracetam is available as anover-the-counter drugunder the name Memoril Mite, and is available in 600 mg pills.

See also

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  • AMPA receptor positive allosteric modulator
  • Aniracetam
  • Brivaracetam—an analogue of piracetam with the same additional side chain as levetiracetam and a three–carbon chain. It exhibits greaterantiepilepticproperties than levetiracetam in animal models, but with a somewhat smaller, although still high, therapeutic range.
  • Ergoloid
  • 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 proteinSV2A.
  • Oxiracetam
  • Phenylpiracetam—a phenylated analog of the drug piracetam which was developed in 1983 in Russia where it is available as a prescription drug.
  • Pramiracetam

References

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