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Racetams are a class of
drugs 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 inhalat ...
that share a pyrrolidone nucleus. Some, such as piracetam, aniracetam,
oxiracetam Oxiracetam (developmental code name ISF 2522) 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 mechan ...
,
pramiracetam Pramiracetam is a central nervous system stimulant and nootropic agent belonging to the racetam family of drugs. It is marketed by Menarini under the brand name Pramistar as a treatment for memory and attention deficits in aging people with neu ...
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 ...
are considered
nootropic Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote re ...
s. Others such as
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 ...
,
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
seletracetam Seletracetam (UCB 44212) is a pyrrolidone-derived drug of the racetam family that is structurally related to levetiracetam (trade name Keppra). It was under development by UCB Pharmaceuticals as a more potent and effective anticonvulsant drug to ...
are
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s.


Mechanism

There is no universally accepted mechanism of action for racetams. Racetams generally show negligible affinity for common central nervous system receptors, but modulation of central
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 ...
s, including
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 ...
and
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 ...
, has been reported. Although aniracetam and
nebracetam Nebracetam is an investigational drug of the racetam family that is a M1 acetylcholine receptor agonist in rats. Its effects in humans have not been studied. See also * Piracetam * Aniracetam * Racetam Racetams are a class of drugs that ...
show affinity for
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 ...
receptors, only
nefiracetam Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats. Effects Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergic, ...
demonstrates nanomolar interactions. Modification of membrane-located mechanisms of central signal transduction is another hypothesis. Like some ampakines, some racetams such as piracetam and aniracetam are positive
allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a Receptor (biochemistry), receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allos ...
s 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 ...
. Racetams are understood to work by allosterically modulating
glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system a ...
s, specifically
AMPA receptors The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the centr ...
, leading to Ca2+ influx that is excitatory. Racetams are posited to enhance memory through interaction with glutamate receptors in the
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 ...
.
Methylphenylpiracetam Methylphenylpiracetam is a derivative of piracetam and a positive allosteric modulator of the sigma-1 receptor. It differs from phenylpiracetam by having a methyl group. E1R is the (4''R'',5''S'') stereoisomer of methylphenylpiracetam. Enantio ...
is a positive allosteric modulator of the
sigma-1 receptor The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gene. ...
.


Cofactors

In studies with aged rats, marked improvement has been observed in cognitive tasks in experimental groups given piracetam. Performance was further increased when piracetam was combined with
choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...
. Evidence in studies with rats has indicated that the potency of piracetam is increased when administered with
choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...
.


List of Racetams


Legality


Australia

All racetams are schedule 4 substances in Australia under the Poisons Standard (February 2020).Poisons Standard February 2020
comlaw.gov.au
A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."


References

{{Racetams Chemical classes of psychoactive drugs