Piracetam

Piracetam is a drug that has efficacy in cognitive disorders, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia; sources differ on its usefulness for dementia.<ref name="(eMC) 2017"/><ref name=Winblad2005/><ref name=Flic2001>Template:Cite journal</ref> Piracetam is sold as a medication in many European countries. Piracetam in the United States is not approved for general use.<ref name=JAMA2019>Template:Cite journal</ref>

Piracetam is in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It is a cyclic derivative of the neurotransmitter GABA<ref name=Winblad2005/> and shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid. Related drugs include the anticonvulsants levetiracetam and brivaracetam, and the putative nootropics aniracetam and phenylpiracetam.

Efficacy

Dementia

A 2001 Cochrane review concluded that there was not enough evidence to support piracetam for dementia or cognitive problems.<ref name=Flic2001/> A 2005 review found some evidence of benefit in older subjects with cognitive impairment.<ref name=Winblad2005>Template:Cite journal</ref> In 2008, a working group of the British Academy of Medical Sciences noted that many of the trials of piracetam for dementia were flawed.<ref>Template:Cite report</ref>

There is insufficient evidence of piracetam as a treatment for vascular dementia.<ref>Template:Cite journal</ref>

Depression and anxiety

Some sources suggest that piracetam's overall effect on lowering depression and anxiety is higher than on improving memory.<ref name="pmid20166767">Template:Cite journal</ref> However, depression is reported to be an occasional adverse effect of piracetam.<ref name="compendium">Nootropil®. Arzneimittel-Kompendium der Schweiz. 2013-09-12. Retrieved 2013-10-27.</ref>

Attention deficit hyperactivity disorder (ADHD)

Several clinical trials have looked at piracetam's efficacy as a treatment for ADHD. Many of these have found that the drug fails to deliver the same therapeutic effects as current standard treatments for the disorder.<ref>Template:Cite web</ref>Template: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 and atomoxetine was more effective than atomoxetine alone.<ref>Template:Cite journal</ref>

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

Piracetam may facilitate the deformability of erythrocytes in capillary which is useful for cardiovascular disease.<ref name=Winblad2005/><ref name="(eMC) 2017"/>

Peripheral vascular effects of piracetam have suggested its use potential for vertigo, dyslexia, Raynaud's phenomenon and sickle cell anemia.<ref name=Winblad2005/><ref name="(eMC) 2017"/> There is no evidence to support piracetam's use in sickle cell crisis prevention<ref>Template:Cite journal</ref> or for fetal distress during childbirth.<ref>Template:Cite journal</ref> There is no evidence for benefit of piracetam with acute ischemic stroke,<ref>Template:Cite journal</ref> though there is debate as to its utility during stroke rehabilitation.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

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.<ref name=Winblad2005/><ref name="(eMC) 2017">Template:Cite web</ref>

Side effects

Symptoms including anxiety, insomnia, irritability, headache, agitation, tremor, and hyperkinesia are occasionally reported.<ref name="compendium" /><ref name="Chouinard, G. 1983 pp.100-106">Template:Cite journal</ref><ref name=pmid342247>Template:Cite journal</ref> Other reported side effects include somnolence, weight gain, clinical depression, weakness, increased libido, and hypersexuality.<ref name="compendium" />

According to a 2005 review, piracetam has been observed to have the following side effects: hyperkinesia, weight gain, anxiety, somnolence, depression, and weakness.<ref name=Winblad2005/>

Piracetam reduces platelet aggregation as well as fibrinogen concentration, and thus is contraindicated to patients with cerebral hemorrhage.<ref name=Winblad2005/><ref name="(eMC) 2017"/>

Toxicity

The Template:LD50 for oral consumption in humans has not been determined.<ref name=noot /> The LD₅₀ is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely low acute toxicity.<ref>Template:Cite web</ref> 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.<ref name=Winblad2005/> 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.<ref name=ahmedoswald>Template:Cite journal</ref> It is hypothesized to act on ion channels or ion carriers, thus leading to increased neuron excitability.<ref name=noot>Template:Cite journal</ref> GABA brain metabolism and GABA receptors are not affected by piracetam<ref>Template:Cite journal</ref>

Piracetam increases the action of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptorsTemplate:Citation needed, which are implicated in memory processes.<ref name=novel>Template:Cite journal</ref> 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.<ref name=novel /><ref>Template:Cite journal</ref> Piracetam may exert its global effect on brain neurotransmission via modulation of ion channels (i.e., Na⁺, K⁺).<ref name=noot /> 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.<ref name="ReferenceA">Template:Cite journal</ref><ref>Template:Cite journal</ref> Piracetam, while in the brain, appears to increase the synthesis of cytochrome b5,<ref>Template:Cite journal</ref> 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.<ref name="ReferenceA"/>

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)<ref name="pmid16343512">Template:Cite journal</ref> is much higher than the concentration necessary to inhibit N-type calcium channels (IC50 of piracetam in rat neurons was 3 μM).<ref name="pmid23045722">Template:Cite journal</ref>

History

Piracetam was first made some time between the 1950s and 1964 by Corneliu E. Giurgea.<ref>Template:Cite book</ref> There are reports of it being used for epilepsy in the 1950s.<ref>Template:Cite book</ref>

Society and culture

In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students.<ref>Template:Cite web</ref>

Legal status

Piracetam is an uncontrolled substance in the United States, meaning it is legal to possess without a license or prescription.<ref>Template:Cite web</ref> 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

In the United States, piracetam is not approved by the Food and Drug Administration.<ref name=drugbank>Template:Cite web</ref> Piracetam is not permitted in compounded drugs or dietary supplements in the United States.<ref name=sbm>Template:Cite web</ref> 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.<ref name=JAMA2019/> 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<ref>Template:Cite web</ref> for adults with myoclonus of cortical origin, irrespective of cause, and should be used in combination with other anti-myoclonic therapies.<ref>Template:Cite web</ref>

In Japan, piracetam is approved as a prescription drug.<ref>Template:Cite web</ref>

In the Czech Republic, piracetam is available without prescription.<ref>Template:Cite web</ref><ref>Template:Cite web</ref>

Piracetam has no DIN in Canada, and thus cannot be sold, but can be imported for personal use in Canada.<ref>Template:Cite web</ref>

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.

See also

• 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 greater antiepileptic properties than levetiracetam in animal models, but with a somewhat smaller, although still high, therapeutic range.
• Ergoloid
• Levetiracetam—an analogue of piracetam bearing an additional ethyl sidechain and bearing antiepileptic pharmacological properties through a poorly understood mechanism probably related to its affinity for the vesicle protein SV2A.
• 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

• Template:Cite web

External links

• Template:Cite journal