Identification
- Summary
Piracetam is a nootropic cyclic GABA derivative used in myoclonus, sickle cell disease, alcohol dependence, and as a general cognitive enhancer.
- Generic Name
- Piracetam
- DrugBank Accession Number
- DB09210
- Background
Piracetam is a nootropic drug in the racetams group, with chemical name 2-oxo-1-pyrrolidine acetamide. It shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid and is a cyclic derivative of the neurotransmitter γ-aminobutyric acid (GABA). However its mechanism of action differ from that of endogenous GABA. Piracetam has neuroprotective and anticonvulsant properties and is reported to improve neural plasticity 1. Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia although the clinical application in these conditions is not yet established. Piracetam has effects on the vascular system by reducing erythrocyte adhesion to the vascular endothelium, hindering vasospasms and facilitating microcirculation 1.
Originally marketed by UCB Pharma in 1971, piracetam was the first nootropic drug to modulate cognitive function without causing sedation or stimulation 1. It is not approved for any medical or dietary use by the FDA. In the UK, piracetam is prescribed mainly for myoclonus, but is used off-label for other conditions such as learning difficulties in children, memory loss or other cognitive defects in the elderly, and sickle-cell vaso-occlusive crises 4. Evidence to support its use for many conditions is unclear.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Piracetam (DB09210)
- Weight
- Average: 142.1558
Monoisotopic: 142.074227574 - Chemical Formula
- C6H10N2O2
- Synonyms
- Piracetam
- Piracetamum
- External IDs
- CL-871
- KT-801
- UCB 6215
Pharmacology
- Indication
Indicated in adult patients suffering from myoclonus of cortical origin, irrespective of aetiology, and should be used in combination with other anti-myoclonic therapies 5.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Alcohol Dependency
- Alcohol Withdrawal Syndrome
- Cognitive Deficits caused by Injuries, Craniocerebral
- Cognitive Dysfunctions
- Cognitive Impairment (CI)
- Comatose caused by Blood Vessel (Vascular) Dysfunction
- Comatose caused by CNS Toxicity
- Comatose caused by Traumas
- Learning Disorders
- Myoclonus
- Sickle Cell Disease (SCD)
- Giddiness caused by Injuries, Craniocerebral
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Piracetam is known to mediate various pharmacodynamic actions:
Neuronal effects:
Piracetam modulates the cholinergic, serotonergic, noradrenergic, and glutamatergic neurotransmission although the drug does not display high affinity to any of the associated receptors (Ki >10μM). Instead, piracetam increases the density of postsynaptic receptors and/or restore the function of these receptors through stabilizing the membrane fluidity 1. In the forebrain of aging mice, the density of NMDA receptors was increased by approximately 20% following 14 days of piracetam treatment. Based on the findings of various animal and human studies, the cognitive processses including learning, memory, attention and consciousness were enhanced from piracetam therapy without inducing sedation and psychostimulant effects 5. Piracetam mediate neuroprotective effects against hypoxia-induced damage, intoxication, and electroconvulsive therapy 5.
In two studies involving alcohol-treated rats with evidences of withdrawal-related neuronal loss, piracetam was shown to reduce the extent of neuronal loss and increase the numbers of synapses in the hippocampus by up to 20% relative to alcohol-treated or alcohol-withdrawn rats 1. This suggests that piracetam is capable in promoting neuroplasticity when recoverable neural circuits are present 1. Although the mechanism of action is not fully understood, administration of piracetam prior to a convulsant stimulus reduces the seizure severity and enhances the anticonvulsant effectiveness of conventional antiepileptics such as carbamazepine and diazepam 3.
Vascular effects:
Piracetam is shown to increase the deformability of erythrocytes, reduce platelet aggregation in a dose-dependent manner, reduce the adhesion of erythrocytes to vascular endothelium and capillary vasospasm. In healthy volunteers, piracetam mediated a direct stimulant effect on prostacycline synthesis and reduced the plasma levels of fibrinogen and von Willebrand’s factors (VIII: C; VIII R: AG; VIII R: vW) by 30 to 40% 5. Potentiated microcirculation is thought to arise from a combination of effects on erythrocytes, blood vessels and blood coagulation 1.
- Mechanism of action
Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity 1. Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide 2. The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion 1. This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function 4 such as membrane transport, chemical secretion, and receptor binding and stimulation 1.
Through restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level 1. It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow 1.
- Absorption
Piracetam displays a linear and time-dependent pharmacokinetic properties with low intersubject variability over a large range of doses. Piracetam is rapidly and extensively absorbed following oral administration with the peak plasma concentration is reached within 1 hour after dosing in fasted subjects. Following a single oral dose of 3.2 g piracetam, the peak plasma concentration (Cmax) was 84 µg/mL. Intake of food may decrease the Cmax by 17% and increase the time to reach Cmax (Tmax) from 1 to 1.5 hours. Tmax in the cerebrospinal fluid is achieved approximately 5 hours post-administration 4.
The absolute bioavailability of piracetam oral formulations is close to 100% and the steady state plasma concentrations are achieved within 3 days of dosing 4.
- Volume of distribution
Vd is approximately 0.6L/kg. Piracetam may cross the blood-brain barrier as it was measured in the cerebrospinal fluid following intravenous administration 4. Piracetam diffuses to all tissues except adipose tissues, crosses placental barrier and penetrates the membranes of isolated red blood cells 4.
- Protein binding
Piracetam is not reported to be bound to plasma proteins 4.
- Metabolism
As large proportion of total piracetam administered is excreted as unchanged drug, there is no known major metabolism of piracetam 4.
- Route of elimination
Piracetam is predominantly excreted via renal elimination, where about 80-100% of the total dose is recovered in the urine. Approximately 90% of the dose of piracetam is excreted in the urine as unchanged drug 4.
- Half-life
The plasma half life of piracetam is approximately 5 hours following oral or intravenous administration. The half life in the cerebrospinal fluid was 8.5 hours 4.
- Clearance
The apparent total body clearance is 80-90 mL/min 4.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The cases of overdose with piracetam is rare. The highest reported overdose with piracetam was oral intake of 75g which was associated with diarrhea and abdominal pain; the signs were most likely related to the extreme high dose of sorbitol contained in the used formulation. In cases of acute, significant overdosage, stomach emptying by gastric lavage or induced emesis is recommended as there are no known antidotes for piracetam 4. Management for an overdose will most likely be symptomatic treatment and may include hemodialysis, where the extraction efficacy of the dialyser is 50 to 60% for the drug 4.
Oral LD50 in a mouse acute toxicity study was 2000 mg/kg MSDS.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Piracetam which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Piracetam which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Piracetam which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Piracetam which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Piracetam which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Piracetam which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Piracetam which could result in a higher serum level. Acrivastine Piracetam may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir Acyclovir may decrease the excretion rate of Piracetam which could result in a higher serum level. Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Piracetam which could result in a higher serum level. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Myocalm (Taiho Pharmaceuticals)
Categories
- ATC Codes
- N06BX03 — Piracetam
- Drug Categories
- Acetamides
- Acetates
- Acids, Acyclic
- Amides
- Central Nervous System Agents
- Compounds used in a research, industrial, or household setting
- Drugs that are Mainly Renally Excreted
- Nervous System
- Neuroprotective Agents
- Nootropic Agents
- Protective Agents
- Psychoanaleptics
- Psychostimulants, Agents Used for ADHD and Nootropics
- Pyrrolidines
- Pyrrolidinones
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acids and derivatives
- Alternative Parents
- Pyrrolidine-2-ones / N-alkylpyrrolidines / Tertiary carboxylic acid amides / Primary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- 2-pyrrolidone / Aliphatic heteromonocyclic compound / Alpha-amino acid or derivatives / Azacycle / Carbonyl group / Carboxamide group / Hydrocarbon derivative / Lactam / N-alkylpyrrolidine / Organic nitrogen compound show 10 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- ZH516LNZ10
- CAS number
- 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)
- IUPAC Name
- 2-(2-oxopyrrolidin-1-yl)acetamide
- SMILES
- NC(=O)CN1CCCC1=O
References
- General References
- Winblad B: Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Rev. 2005 Summer;11(2):169-82. [Article]
- Kurz C, Ungerer I, Lipka U, Kirr S, Schutt T, Eckert A, Leuner K, Muller WE: The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide. Br J Pharmacol. 2010 May;160(2):246-57. doi: 10.1111/j.1476-5381.2010.00656.x. Epub 2010 Mar 9. [Article]
- Fischer W, Kittner H, Regenthal R, Russo E, De Sarro G: Effects of piracetam alone and in combination with antiepileptic drugs in rodent seizure models. J Neural Transm (Vienna). 2004 Sep;111(9):1121-39. doi: 10.1007/s00702-004-0155-6. Epub 2004 May 14. [Article]
- Nootropil tablets Drug Summary [Link]
- electronic Medicines Compendium (eMC): Nootripil Summary of Product Characteristics [Link]
- External Links
- ChemSpider
- 4677
- BindingDB
- 62877
- 8351
- ChEBI
- 32010
- ChEMBL
- CHEMBL36715
- ZINC
- ZINC000003812874
- PDBe Ligand
- PZI
- Wikipedia
- Piracetam
- PDB Entries
- 3lsf / 3lsl / 3lsx
- MSDS
- Download (47.2 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Vertigo, Peripheral 1 4 Terminated Treatment Acute Ischemic Stroke of the Middle Cerebral Artery 1 3 Completed Treatment Tardive Dyskinesia (TD) 1 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 3 Withdrawn Treatment Post-Poliomyelitis Syndrome 1 1 Completed Treatment Cocaine Related Disorders 1 1 Withdrawn Treatment Cocaine Related Disorders 1 Not Available Completed Not Available Alzheimer's Disease (AD) / Dementia / Vascular Dementia (VaD) 1 Not Available Completed Treatment Memory Disorders 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous Solution Intravenous 1 gr/5ml Syrup Oral 200 mg/ml Tablet Oral Solution / drops Oral Injection Intravenous 200 MG/ML Tablet, film coated Oral Powder, for solution Oral Solution 200 mg/1ml Syrup Oral Granule Oral Syrup Oral 8 g Tablet Oral 800 mg Injection, solution Intravenous 1 g/5ml Tablet Oral 1200 MG Injection, solution Parenteral 3 G Solution Parenteral 12 g/60ml Injection, solution 12 G/60ML Solution Intravenous; Oral Solution Intravenous; Oral 3 G/15ML Solution Oral 20 % Solution / drops Oral 33.33 % Injection Intramuscular; Intravenous 1 gr Syrup Oral 200 ml Injection, solution Parenteral 3 g/15ml Solution Conjunctival; Ophthalmic 0.2 g Injection Parenteral 3 g Syrup Oral 20 g Solution Oral 20 g/100ml Powder Oral 48 g Tablet, film coated Oral 1200.00 mg Tablet, film coated Oral 800.00 mg Tablet, coated Oral 1200 mg Injection Parenteral Injection, solution Intravenous 1 mg/5ml Injection Intramuscular; Intravenous 1 gr/5ml Solution Oral Injection, solution Intramuscular; Intravenous Tablet, extended release Oral Tablet, film coated Oral 800000 MG Injection, solution Injection, solution 3 G/15ML Solution Oral 333.3 mg/ml Solution Parenteral 1 g/5ml Solution Oral 33 % Granule Oral 2.4 G Injection, solution 1 g/5ml Tablet Oral 0.8 g Granule, for solution Oral Granule, for suspension Oral Injection Injection, solution Intravenous Injection Intramuscular; Intravenous Capsule Oral Tablet, coated Oral 800 mg Capsule Oral 400 mg Tablet, film coated Oral 1200 mg Tablet, film coated Oral 800 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 152 MSDS boiling point (°C) Decomposes MSDS - Predicted Properties
Property Value Source Water Solubility 479.0 mg/mL ALOGPS logP -1.6 ALOGPS logP -1.7 Chemaxon logS 0.53 ALOGPS pKa (Strongest Acidic) 15.93 Chemaxon pKa (Strongest Basic) -2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.4 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 35.06 m3·mol-1 Chemaxon Polarizability 13.96 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Drug created at October 20, 2015 19:46 / Updated at May 07, 2021 21:06