Piracetam is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

marketed as a treatment for

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...

. It is also used as a cognitive enhancer to improve memory, attention, and learning. Evidence to support its use is unclear, with some studies showing modest benefits in specific populations and others showing minimal or no benefit. 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. Piracetam is in the

racetam 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 ant ...

s group, with chemical name ''2-oxo-1-pyrrolidine acetamide''. It is a derivative of the neurotransmitter GABA and shares the same 2-oxo-pyrrolidone base structure with

pyroglutamic acid Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but little studied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam. The names of pyroglutamic ac ...

. Piracetam is a cyclic derivative of GABA (gamma-aminobutyric acid). Related drugs include the anticonvulsants

levetiracetam Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formu ...

and

brivaracetam Brivaracetam, sold under the brand names Briviact and Brivajoy among others, a chemical analog of levetiracetam, is a racetam derivative with anticonvulsant (antiepileptic) properties. It is marketed by the pharmaceutical company UCB. It is av ...

, and the putative nootropics aniracetam and

phenylpiracetam Phenylpiracetam ( INN: fonturacetam, brand names Phenotropil Фенотропил, Carphedon), is a phenylated analog of the drug piracetam. It was developed in 1983 as a medication for Soviet Cosmonauts to treat the prolonged stresses of wor ...

Efficacy

Dementia

A 2001

Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...

concluded that there was not enough evidence to support piracetam for

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

or cognitive problems. A 2005 review found some evidence of benefit in older subjects with cognitive impairment. In 2008, a working group of the British

Academy of Medical Sciences The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society. Its mission is to adv ...

noted that many of the trials of piracetam for dementia were flawed. There is no good evidence that piracetam is of benefit in treating

vascular dementia Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisti ...

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.Nootropil®
Arzneimittel-Kompendium der Schweiz. 2013-09-12. Retrieved 2013-10-27.

Other

Piracetam may facilitate the deformability of erythrocytes in

capillary A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

which is useful for cardiovascular disease. Peripheral vascular effects of piracetam have suggested its use potential for

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

dyslexia Dyslexia, also known until the 1960s as word blindness, is a disorder characterized by reading below the expected level for one's age. Different people are affected to different degrees. Problems may include difficulties in spelling words, r ...

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

and

sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...

. There is no evidence to support piracetam's use in sickle cell crisis prevention or for

fetal distress Fetal distress, also known as non-reassuring fetal status, is a condition during pregnancy or labor in which the fetus shows signs of inadequate oxygenation. Due to its imprecision, the term "fetal distress" has fallen out of use in American obstetr ...

during childbirth. There is no evidence for benefit of piracetam with ''acute'' ischemic stroke, though there is debate as to its utility during stroke rehabilitation.

Anti-vasospasm

Piracetam has been found to diminish

erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can be ...

to vascular wall

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

, making any

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or ...

in the

less severe. This contributes to its efficacy in promoting

microcirculation The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...

, including to the brain and kidneys.

Side effects

Symptoms of general excitability, including

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, agitation,

nervousness Nervous may refer to: * nervousness * Nervous system, a network of cells in an animal's body that coordinates movement and the senses ** Nervous tissue, the cells of the nervous system that work in aggregate to transmit signals Music * "Nervous" ...

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...

, and

hyperkinesia Hyperkinesia refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. Hyperkinesia is a state of excessive restlessness which is featured in a large variet ...

, are occasionally reported. Other reported side effects include

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs wh ...

clinical depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

, increased

libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...

, and

hypersexuality Hypersexuality is extremely frequent or suddenly increased libido. It is controversial whether it should be included as a clinical diagnosis used by mental healthcare professionals. Nymphomania and satyriasis were terms previously used for the c ...

. According to a 2005 review, piracetam has been observed to have the following side effects: hyperkinesia, weight gain, nervousness, somnolence, depression and asthenia. Piracetam reduces

platelet aggregation Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

as well as

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...

concentration, and thus is contraindicated to patients with cerebral hemorrhage.

Toxicity

The for oral consumption in humans has not been determined. The LD₅₀ is 5.6 g/kg for rats and 20 g/kg for mice, indicating extremely low

acute toxicity Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time (usually less than 24 hours). To be described as ''acute'' toxicity, the adverse effect ...

. 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 In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

, as with

s 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 In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

of the

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...

, although this action is very weak and its clinical effects may not necessarily be mediated by this action. 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 Piracetam improves the function of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

via

muscarinic Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...

(ACh)

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

, which are implicated in

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...

processes. Furthermore, piracetam may have an effect on

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

receptors, which are involved with

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, attitudes, and preferences. The ability to learn is possessed by humans, animals, and some machine learning, machines ...

and

processes. Piracetam is thought to increase cell membrane permeability. Piracetam may exert its global effect on brain neurotransmission via modulation of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

s (''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 Adenylate kinase ( ECbr>2.7.4.3 (also known as ADK or myokinase) is a phosphotransferase enzyme that catalyzes the interconversion of the various adenosine phosphates (ATP, ADP, and AMP). By constantly monitoring phosphate nucleotide levels insid ...

in rat brains. Piracetam, while in the brain, appears to increase the synthesis of

cytochrome b5 Cytochromes ''b''5 are ubiquitous electron transport hemoproteins found in animals, plants, fungi and purple phototrophic bacteria. The microsomal and mitochondrial variants are membrane-bound, while bacterial and those from erythrocytes and ot ...

, which is a part of the

electron transport An electron transport chain (ETC) is a series of protein complexes and other molecules that transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples thi ...

mechanism in

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

. But in the brain, it also increases the permeability of some intermediates of the

Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

through the mitochondrial outer membrane. Piracetam inhibits

N-type calcium channel N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the prima ...

s. The concentration of piracetam achieved in

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

after a typical dose of 1200 mg (about 100 μM) is much higher than the concentration necessary to inhibit

s (

IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...

of piracetam in rat neurons was 3 μM).

History

Piracetam was first made some time between the 1950s and 1964 by Corneliu E. Giurgea. There are reports of it being used for epilepsy in the 1950s.

Society and culture

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

Legal status

Piracetam is an uncontrolled substance in the United States meaning it is legal to possess without a license or prescription.

Regulatory status

In the United States, piracetam is not approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

. Piracetam is not permitted in compounded drugs or dietary supplements in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

. Like most research chemicals, it has been available over-the-counter, self-regulated, and third-party lab tested by many US companies for decades. In the United Kingdom, piracetam is approved as a prescription drug Prescription Only Medicine (POM) number is PL 20636/2524 for adult with myoclonus of cortical origin, irrespective of cause, and should be used in combination with other anti-myoclonic therapies. In Japan piracetam is approved as a prescription drug. Piracetam has no DIN in Canada, and thus cannot be sold but can be imported for personal use in Canada. 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 Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs A prescription drug (also prescription medication or prescripti ...

under the name Memoril Mite, and is available in 600 mg pills.

References

External links

* {{Ionotropic glutamate receptor modulators Acetamides AMPA receptor positive allosteric modulators Racetams Nootropics