Oxiracetam

Last Updated: September 28 2022

Oxiracetam is one of the three first-tier racetam compounds, being produced after both Piracetam and Aniracetam. Oxiracetam appears to enhance the release of excitatory neurotransmitters and can aid in memory formation, but lacks human studies.

Oxiracetam is most often used for

Summary

Oxiracetam is one of the racetams, and is structurally different from piracetam due to a single hydroxyl group. It is also used for nootropic purposes such as enhancing learning in students or preventing against cognitive decline. Like all other racetams, it is a synthetic molecule that is not found in food sources or in nature.

When looking at the evidence for oxiracetam at this point in time it seems to have a fair bit of human evidence for reducing the rate of organic cognitive decline (a natural loss in cognition that occurs during the aging process that is not associated with any disease state) and with dementia, yet the lone study in persons with Alzheimer's showed no apparent benefit with oxiracetam supplementation. When it does aid in cognitive decline, it is somewhat comparable in potency to Alpha-GPC and seems to be slightly more potent than piracetam.

There is currently no evidence to support cognitive enhancement of oxiracetam in young humans with no cognitive impairment looking to increase memory formation.

When looking at animal evidence, oxiracetam appears to very reliably and potently prevent amnesia induced by a variety of anti-cholinergic or anti-glutaminergic compounds (injections of 3-30mg/kg in rats pretty much normalizing memory formation). It has been implicated in increasing memory formation in otherwise healthy and young rats/mice with no apparent cognitive impairment (suggesting that it can be used as a nootropic) but it appears to require at least a five day loading period.

Oxiracetam is a positive AMPA modulator similar in mechanism and potency (but not binding site) to both piracetam and aniracetam but may have an additional benefit of increasing glutamate, acetylcholine, and D-aspartic acid release from activated but not resting neurons. This two-fold sequence (enhancing glutamate release and then positively modulating one of the receptors it signals through) ultimately increases metabolic activity in neuronal cells and memory formation.

What else is Oxiracetam known as?
Note that Oxiracetam is also known as:
  • 4-hydroxy-2-oxo-pyrrolidinoacetamide
  • ISF-2522
Oxiracetam should not be confused with:
Dosage information

Supplementation of Oxiracetam tends to be in the dosage range of 1,200-2,400mg taken over the course of a day, either in two to three evenly spread dosing periods (such as three doses of 400mg or 800mg).

No studies have assessed whether or not oxiracetam would benefit from being taken with a meal, but it should be taken approximately one hour prior to a learning activity.

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References
3.^Pellegata R, Pinza M, Pifferi G, Gaiti A, Mozzi R, Tirillini B, Porcellati GCyclic GABA-GABOB analogues. III - Synthesis and biochemical activity of new alkyl and acyl derivatives of 4-hydroxy-2-pyrrolidinoneFarmaco Sci.(1981 Oct)
4.^Copani A, Genazzani AA, Aleppo G, Casabona G, Canonico PL, Scapagnini U, Nicoletti FNootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal culturesJ Neurochem.(1992 Apr)
6.^Banfi S, Fonio W, Allievi E, Pinza M, Dorigotti LCyclic GABA-GABOB analogues. IV. Activity on learning and memoryFarmaco Sci.(1984 Jan)
7.^Son J, Lee J, Lee M, Lee E, Lee JH, La S, Kim DHRapid quantitative analysis of oxiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometryJ Pharm Biomed Anal.(2004 Nov 15)
13.^Davies SN, Lester RA, Reymann KG, Collingridge GLTemporally distinct pre- and post-synaptic mechanisms maintain long-term potentiationNature.(1989 Apr 6)
17.^Sugiyama H, Ito I, Hirono CA new type of glutamate receptor linked to inositol phospholipid metabolismNature.(1987 Feb 5-11)
19.^Yoshii M, Watabe S, Murashima YL, Nukada T, Shiotani TCellular mechanism of action of cognitive enhancers: effects of nefiracetam on neuronal Ca2+ channelsAlzheimer Dis Assoc Disord.(2000)
21.^Magnani M, Pozzi O, Biagetti R, Banfi S, Dorigotti LOxiracetam antagonizes the disruptive effects of scopolamine on memory in the radial mazePsychopharmacology (Berl).(1992)
22.^Mondadori C, Classen W, Borkowski J, Ducret T, Buerki H, Schadé AEffects of oxiracetam on learning and memory in animals: comparison with piracetamClin Neuropharmacol.(1986)
25.^Cavoy A, Van Golf-Racht B, Delacour JRelationships between arousal and cognition-enhancing effects of oxiracetamPharmacol Biochem Behav.(1994 Feb)
26.^Castellano C, Battaglia M, Sansone MOxiracetam prevents haloperidol-induced passive avoidance impairment in micePharmacol Biochem Behav.(1992 Aug)
28.^Mondadori C, Hengerer B, Ducret T, Borkowski JDelayed emergence of effects of memory-enhancing drugs: implications for the dynamics of long-term memoryProc Natl Acad Sci U S A.(1994 Mar 15)
29.^Sansone M, Castellano C, Ammassari-Teule MImprovement of avoidance acquisition by the nootropic drug oxiracetam in miceArch Int Pharmacodyn Ther.(1985 May)
30.^Sansone M, Oliverio AAvoidance facilitation by nootropicsProg Neuropsychopharmacol Biol Psychiatry.(1989)
34.^Belfiore P, Ponzio F, Biagetti R, Berettera C, Magnani M, Pozzi OOxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7Neurosci Lett.(1992 Aug 31)
36.^Pittaluga A, Pattarini R, Raiteri MPutative cognition enhancers reverse kynurenic acid antagonism at hippocampal NMDA receptorsEur J Pharmacol.(1995 Jan 16)
37.^Preda L, Alberoni M, Bressi S, Cattaneo C, Parini J, Canal N, Franceschi MEffects of acute doses of oxiracetam in the scopolamine model of human amnesiaPsychopharmacology (Berl).(1993)
38.^Baumel B, Eisner L, Karukin M, MacNamara R, Katz RJ, Deveaugh-Geiss JOxiracetam in the treatment of multi-infarct dementiaProg Neuropsychopharmacol Biol Psychiatry.(1989)
39.^Dysken MW, Katz R, Stallone F, Kuskowski MOxiracetam in the treatment of multi-infarct dementia and primary degenerative dementiaJ Neuropsychiatry Clin Neurosci.(1989 Summer)
40.^Maina G, Fiori L, Torta R, Fagiani MB, Ravizza L, Bonavita E, Ghiazza B, Teruzzi F, Zagnoni PG, Ferrario E, et alOxiracetam in the treatment of primary degenerative and multi-infarct dementia: a double-blind, placebo-controlled studyNeuropsychobiology.(1989)
41.^Bottini G, Vallar G, Cappa S, Monza GC, Scarpini E, Baron P, Cheldi A, Scarlato GOxiracetam in dementia: a double-blind, placebo-controlled studyActa Neurol Scand.(1992 Sep)
42.^Green RC, Goldstein FC, Auchus AP, Presley R, Clark WS, Van Tuyl L, Green J, Hersch SM, Karp HRTreatment trial of oxiracetam in Alzheimer's diseaseArch Neurol.(1992 Nov)
43.^Nicoletti F, Casabona G, Genazzani AA, Copani A, Aleppo G, Canonico PL, Scapagnini UExcitatory amino acids and neuronal plasticity: modulation of AMPA receptors as a novel substrate for the action of nootropic drugsFunct Neurol.(1992 Sep-Oct)
44.^Fallarino F, Genazzani AA, Silla S, L'Episcopo MR, Camici O, Corazzi L, Nicoletti F, Fioretti MC{3H}aniracetam binds to specific recognition sites in brain membranesJ Neurochem.(1995 Aug)
45.^Pittaluga A, Pattarini R, Andrioli GC, Viola C, Munari C, Raiteri MActivity of putative cognition enhancers in kynurenate test performed with human neocortex slicesJ Pharmacol Exp Ther.(1999 Jul)
47.^Ketchum JS, Sidell FR, Crowell EB Jr, Aghajanian GK, Hayes AH JrAtropine, scopolamine, and ditran: comparative pharmacology and antagonists in manPsychopharmacologia.(1973 Jan 1)
49.^Spignoli G, Pedata F, Giovannelli L, Banfi S, Moroni F, Pepeu GEffect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisitionClin Neuropharmacol.(1986)
50.^Pavlík A, Benesová O, Dlohozková NEffects of nootropic drugs on brain cholinergic and dopaminergic transmissionAct Nerv Super (Praha).(1987 Mar)
52.^Pittaluga A, Vaccari D, Raiteri MThe "kynurenate test", a biochemical assay for putative cognition enhancersJ Pharmacol Exp Ther.(1997 Oct)
53.^Gozzani JL, Izquierdo IPossible peripheral adrenergic and central dopaminergic influences in memory consolidationPsychopharmacology (Berl).(1976 Aug 26)
54.^Oei TP, King MGCatecholamines and aversive learning: a reviewNeurosci Biobehav Rev.(1980 Summer)
56.^Lee DS, Ryu HJ, Kim JE, Choi HC, Kim YI, Song HK, Kang TCThe effect of levetiracetam on status epilepticus-induced neuronal death in the rat hippocampusSeizure.(2013 Jun)
58.^Lenègre A, Chermat R, Avril I, Stéru L, Porsolt RDSpecificity of piracetam's anti-amnesic activity in three models of amnesia in the mousePharmacol Biochem Behav.(1988 Mar)
61.^Feldman RG, White RF, Eriator IITrimethyltin encephalopathyArch Neurol.(1993 Dec)
62.^Scallet AC, Pothuluri N, Rountree RL, Matthews JCQuantitating silver-stained neurodegeneration: the neurotoxicity of trimethlytin (TMT) in aged ratsJ Neurosci Methods.(2000 May 15)
65.^Gabryel B, Trzeciak HI, Pudełko A, Cieślik PInfluence of piracetam and oxiracetam on the content of high-energy phosphates and morphometry of astrocytes in vitroPol J Pharmacol.(1999 Nov-Dec)
67.^Sansone M, Castellano C, Battaglia M, Ammassari-Teule MEffects of oxiracetam-nicotine combinations on active and passive avoidance learning in micePharmacol Biochem Behav.(1991 May)
68.^Sansone M, Castellano C, Palazzesi S, Battaglia M, Ammassari-Teule MEffects of oxiracetam, physostigmine, and their combination on active and passive avoidance learning in micePharmacol Biochem Behav.(1993 Feb)