oxiracetam
{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464373213
| IUPAC_name = (RS)-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide
| image = Oxiracetam.svg
| image_class = skin-invert-image
| width = 120px
| image2 = Oxiracetam.png
| image_class2 = bg-transparent
| width2 = 120px
| chirality = Racemic mixture
| tradename =
| pregnancy_category =
| legal_AU = S4
| legal_US = Unscheduled
| routes_of_administration = Oral, IV{{cite web |title=Oxiracetam for Injection, Package Insert |url=https://www.e-cspc.com/upload/%E6%98%8E%E6%98%9F%E4%BA%A7%E5%93%81/files/%E6%B3%A8%E5%B0%84%E7%94%A8%E5%A5%A5%E6%8B%89%E8%A5%BF%E5%9D%A6.pdf |website=CSPC Pharmaceutical Group}}
| bioavailability = 56-82%
| metabolism =
| elimination_half-life = 8 hours
| excretion = Renal
| onset = 30-90 Minutes
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 62613-82-5
| ATC_prefix = N06
| ATC_suffix = BX07
| PubChem = 4626
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4465
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = P7U817352G
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07346
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 36633
| C=6 | H=10 | N=2 | O=3
| smiles = O=C(N)CN1C(=O)CC(O)C1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IHLAQQPQKRMGSS-UHFFFAOYSA-N
}}
Oxiracetam (developmental code name ISF 2522) is a nootropic drug of the racetam family and a very mild stimulant.{{cite journal | vauthors = Malykh AG, Sadaie MR | title = Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders | journal = Drugs | volume = 70 | issue = 3 | pages = 287–312 | date = February 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000 | s2cid = 12176745 }}{{cite journal | vauthors = Valzelli L, Baiguerra G, Giraud O | title = Difference in learning and retention by Albino Swiss mice. Part III. Effect of some brain stimulants | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 8 | issue = 6 | pages = 337–41 | date = June 1986 | pmid = 3736279 }} Several studies suggest that the substance is safe even when high doses are consumed for a long period of time.{{cite journal | vauthors = Parnetti L, Mecocci P, Petrini A, Longo A, Buccolieri A, Senin U | title = Neuropsychological results of long-term therapy with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia in comparison with a control group | journal = Neuropsychobiology | volume = 22 | issue = 2 | pages = 97–100 | year = 1989 | pmid = 2518332 | doi = 10.1159/000118599 }}{{cite journal | vauthors = Itil TM, Menon GN, Songar A, Itil KZ | title = CNS pharmacology and clinical therapeutic effects of oxiracetam | journal = Clinical Neuropharmacology | volume = 9 | pages = S70-2 | year = 1986 | issue = Suppl 3 | pmid = 3594458 | doi = 10.1097/00002826-198609003-00011 }}{{cite journal | vauthors = Perucca E, Parini J, Albrici A, Visconti M, Ferrero E | title = Oxiracetam pharmacokinetics following single and multiple dose administration in the elderly | journal = European Journal of Drug Metabolism and Pharmacokinetics | volume = 12 | issue = 2 | pages = 145–8 | year = 1987 | pmid = 3691580 | doi = 10.1007/bf03189889 | s2cid = 11415210 }} 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.
Clinical findings
Oxiracetam has been studied to determine if it has an effect on symptoms of dementia,{{cite journal | vauthors = Gouliaev AH, Senning A | title = Piracetam and other structurally related nootropics | journal = Brain Research. Brain Research Reviews | volume = 19 | issue = 2 | pages = 180–222 | date = May 1994 | pmid = 8061686 | doi = 10.1016/0165-0173(94)90011-6 | s2cid = 18122566 }} but no consistent results were obtained in patients with Alzheimer's dementia or organic solvent abuse.
Patients with mild to moderate dementia experienced some beneficial effects, measured by higher scores on tests for logical performance, attention, concentration, memory and spatial orientation. Improvement was also seen in patients with exogenic post-concussion syndrome, organic brain syndromes and other dementias. It seem to be ineffective for enhancing memory and cognitive function in patients with mild to moderate TBI.{{cite journal | vauthors = Liu T, Liu M, Nie M, Zhao Z, Liu X, Qian Y, Yu Y, Sha Z, Wu C, Yuan J, Jiang W, Lv C, Mi L, Tian Y, Zhang J, Jiang R | title = Effect of l-oxiracetam and oxiracetam on memory and cognitive impairment in mild-to-moderate traumatic brain injury patients: Study protocol for a randomized controlled trial | journal = Aging Medicine | volume = 7 | issue = 3 | pages = 341–349 | date = June 2024 | pmid = 38975302 | pmc = 11222749 | doi = 10.1002/agm2.12335 }}
Oxiracetam-treated laboratory mice demonstrated a significant increase in spatial learning performance as determined by the Morris water navigation task, compared to controls. This increase in performance was correlated to an increase in membrane-bound PKC.{{cite journal | vauthors = Fordyce DE, Clark VJ, Paylor R, Wehner JM | title = Enhancement of hippocampally-mediated learning and protein kinase C activity by oxiracetam in learning-impaired DBA/2 mice | journal = Brain Research | volume = 672 | issue = 1–2 | pages = 170–6 | date = February 1995 | pmid = 7749739 | doi = 10.1016/0006-8993(94)01389-y | s2cid = 13191058 }}
Pharmacokinetics
Oxiracetam is well absorbed from the gastrointestinal tract with a bioavailability of 56-82%.
Peak serum levels are reached within one to three hours after a single 800 mg or 2000 mg oral dose, with the maximal serum concentration reaching between 19 and 31 μg/ml at these doses.
Oxiracetam is mainly cleared renally and approximately 84% is excreted unchanged in the urine.
The half-life of oxiracetam in healthy individuals is about 8 hours, whereas it is 10–68 hours in patients with renal impairment.
There is some penetration of the blood–brain barrier with brain concentrations reaching 5.3% of those in the blood (measured one hour after a single 2000 mg intravenous dose).
Clearance rates range from 9 to 95 ml/min and steady-state concentrations when 800 mg is given twice daily range from 60 μM to 530 μM.
The highest brain concentrations of oxiracetam are found in the septum pellucidum, followed by the hippocampus, the cerebral cortex and with the lowest concentrations in the striatum after a 200 mg/kg oral dose given to rats. Oxiracetam may be quantitated in plasma, serum or urine by liquid chromatography with one of several different detection techniques.{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 10th | publisher = Biomedical Publications | location = Seal Beach, CA | date = 2014 | pages = 1524–1525 }}
The major metabolites of Oxiracetam include: beta-hydroxy-2-pyrrolidone, N-aminoacetyl-GABOB, GABOB (beta-hydroxy-GABA) and glycine.{{Citation needed|date=May 2018}} Thus its metabolic route is exactly parallel to that of piracetam, aniracetam, phenylpiracetam, and all other members of the -racetam family, and also pyroglutamic acid.
References
{{Reflist}}
Further reading
{{refbegin}}
- {{cite journal | vauthors = Bottini G, Vallar G, Cappa S, Monza GC, Scarpini E, Baron P, Cheldi A, Scarlato G | title = Oxiracetam in dementia: a double-blind, placebo-controlled study | journal = Acta Neurologica Scandinavica | volume = 86 | issue = 3 | pages = 237–241 | date = September 1992 | pmid = 1414239 | doi = 10.1111/j.1600-0404.1992.tb05077.x | s2cid = 9368980 | doi-access = free }}
- {{cite journal | vauthors = Li W, Liu H, Jiang H, Wang C, Guo Y, Sun Y, Zhao X, Xiong X, Zhang X, Zhang K, Nie Z, Pu X | title = (S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 10052 | date = August 2017 | pmid = 28855592 | pmc = 5577264 | doi = 10.1038/s41598-017-10283-4 | bibcode = 2017NatSR...710052L | doi-access = free }}
- {{cite journal | vauthors = Villardita C, Grioli S, Lomeo C, Cattaneo C, Parini J | title = Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree | journal = Neuropsychobiology | volume = 25 | issue = 1 | pages = 24–28 | date = 1992 | pmid = 1603291 | doi = 10.1159/000118805 }}
- {{cite journal | vauthors = Mondadori C, Classen W, Borkowski J, Ducret T, Buerki H, Schadé A | title = Effects of oxiracetam on learning and memory in animals: comparison with piracetam | journal = Clinical Neuropharmacology | volume = 9 Suppl 3 | issue = Supp.3 | pages = S27-S38 | date = 1986 | pmid = 3594453 | doi = 10.1097/00002826-198609003-00006 }}
- {{cite journal | vauthors = Hu S, Shi J, Xiong W, Li W, Fang L, Feng H | title = Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude | journal = Brain and Behavior | volume = 7 | issue = 10 | pages = e00762 | date = October 2017 | pmid = 29075554 | pmc = 5651378 | doi = 10.1002/brb3.762 | doi-access = free }}
- {{cite journal | vauthors = Krylova IN, Antonova LV, Kamenskiĭ AA, Iasnetsov VV | title = [A comparative study of the nootropic properties of piracetam and oxiracetam] | journal = Farmakologiia I Toksikologiia | volume = 54 | issue = 1 | pages = 14–16 | date = 1991 | pmid = 1860490 }}
{{refend}}
External links
- [https://psychonautwiki.org/wiki/Oxiracetam Oxiracetam on PsychonautWiki]
{{Racetams}}
{{Stimulants}}
{{Ionotropic glutamate receptor modulators}}
Category:AMPA receptor positive allosteric modulators