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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 |
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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 |
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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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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. [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 the FDA, so it is legally sold for research use only. [6]
Piracetam is in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It is a cyclic derivative of the neurotransmitter GABA [4] 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.
A 2001 Cochrane review concluded that there was not enough evidence to support piracetam for dementia or 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 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]
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]
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. [11] 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. [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.
Piracetam may facilitate the deformability of erythrocytes in capillary which is useful for cardiovascular disease. [4] [3]
Peripheral vascular effects of piracetam have suggested its use potential for vertigo, dyslexia, Raynaud's phenomenon and sickle cell anemia. [4] [3] There is no evidence to support piracetam's use in sickle cell crisis prevention [13] or for fetal distress during childbirth. [14] There is no evidence for benefit of piracetam with acute ischemic stroke, [15] though there is debate as to its utility during stroke rehabilitation. [16] [17]
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. [4] [3]
Symptoms of general excitability, including anxiety, insomnia, irritability, headache, agitation, nervousness, tremor, and hyperkinesia, are occasionally reported. [10] [18] [19] 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. [4]
Piracetam reduces platelet aggregation as well as fibrinogen concentration, and thus is contraindicated to patients with cerebral hemorrhage. [4] [3]
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.
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. [4] 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 increases the action 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]
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]
In 2009 piracetam was reportedly popular as a cognitive enhancement drug among students. [33]
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.
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] Like most research chemicals, it has been available over-the-counter, self-regulated, and third-party lab tested by many US companies for decades. [6] Yet, 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 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]
In Czech Republic piracetam is available without prescription. [39] [40]
Piracetam has no DIN in 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 an over-the-counter drug under the name Memoril Mite, and is available in 600 mg pills.
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by executive dysfunction occasioning symptoms of inattention, hyperactivity, impulsivity and emotional dysregulation that are excessive and pervasive, impairing in multiple contexts, and developmentally-inappropriate.
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a potent central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines, alleviating the executive functioning deficits of sustained attention, inhibition, working memory, reaction time and emotional self-regulation.
Atomoxetine, sold under the brand name Strattera, is a selective norepinephrine reuptake inhibitor medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, cognitive disengagement syndrome. It may be used alone or along with psychostimulants. It enhances the executive functions of self-motivation, sustained attention, inhibition, working memory, reaction time and emotional self-regulation. Use of atomoxetine is only recommended for those who are at least six years old. It is taken orally. The effectiveness of atomoxetine is comparable to the commonly prescribed stimulant medication methylphenidate.
Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.
Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth or via a transdermal patch.
Aniracetam, also known as N-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in the United States as a prescription medication or dietary supplement. Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.
Oxiracetam is a nootropic drug of the racetam family and a very mild stimulant. Several studies suggest that the substance is safe even when high doses are consumed for a long period of time. However, the mechanism of action of the racetam drug family is still a matter of research. Oxiracetam is not approved by Food and Drug Administration for any medical use in the United States.
Fasoracetam is a research chemical of the racetam family. It is a putative nootropic that failed to show sufficient efficacy in clinical trials for vascular dementia. It is currently being studied for its potential use for attention deficit hyperactivity disorder.
Galantamine is a type of acetylcholinesterase inhibitor. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis, Galanthus caucasicus, Galanthus woronowii, and other members of the family Amaryllidaceae, such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata. It can also be produced synthetically.
Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem-solving. Neurocognitive disorders include delirium, mild neurocognitive disorders, and major neurocognitive disorder. They are defined by deficits in cognitive ability that are acquired, typically represent decline, and may have an underlying brain pathology. The DSM-5 defines six key domains of cognitive function: executive function, learning and memory, perceptual-motor function, language, complex attention, and social cognition.
Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.
Racetams are a class of drugs that share a pyrrolidone nucleus. Some, such as piracetam, aniracetam, oxiracetam, pramiracetam and phenylpiracetam are considered nootropics. Others such as levetiracetam, brivaracetam, and seletracetam are anticonvulsants.
Viloxazine, sold under the brand name Qelbree among others, is a selective norepinephrine reuptake inhibitor medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30 years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is taken orally. It was used as an antidepressant in an immediate-release form and is used in ADHD in an extended-release form, latterly with comparable effectiveness to atomoxetine and methylphenidate.
Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure. Guanfacine is FDA-approved for monotherapy treatment of ADHD, as well as being used for augmentation of other treatments, such as stimulants. Guanfacine is also used off-label to treat tic disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).
Nicergoline, sold under the brand name Sermion among others, is an ergot derivative used to treat senile dementia and other disorders with vascular origins. Internationally it has been used for frontotemporal dementia as well as early onset in Lewy body dementia and Parkinson's dementia. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It has similar vasoactive properties in other areas of the body, particularly the lungs. Unlike many other ergolines, such as ergotamine, nicergoline is not associated with cardiac fibrosis.
Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for ADHD. Approaches that have been evaluated in the management of ADHD symptoms include FDA-approved pharmacologic treatment and other pharmaceutical agents, psychological or behavioral approaches, combined pharmacological and behavioral approaches, cognitive training, neurofeedback, neurostimulation, physical exercise, nutrition and supplements, integrative medicine, parent support, and school interventions. Based on two 2024 systematic reviews of the literature, FDA-approved medications and to a lesser extent psychosocial interventions have been shown to improve core ADHD symptoms compared to control groups.
Ispronicline is an experimental drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease, but is no longer under development.
N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline. Other names include the brand name Noopept, developmental code GVS-111, and proposed INN omberacetam.
Sunifiram is an experimental drug which has antiamnesic effects in animal studies and with significantly higher potency than piracetam. Sunifiram is a molecular simplification of unifiram (DM-232). Another analogue is sapunifiram (MN-19). As of 2016, sunifiram had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world.
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.