Misplaced Pages

Oxiracetam: Difference between revisions

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
Browse history interactively← Previous editContent deleted Content addedVisualWikitext
Revision as of 15:33, 23 November 2011 editBobber0001 (talk | contribs)Extended confirmed users568 edits Huge revision, tons of information, mostly from one source though← Previous edit Latest revision as of 22:02, 27 September 2024 edit undoAnastrophe (talk | contribs)Extended confirmed users, Pending changes reviewers, Rollbackers21,504 edits →Clinical findings: egregious syntax, clutter. specific strain of mouse not critical to general readership. 
(137 intermediate revisions by 73 users not shown)
Line 1: Line 1:
{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
⚫ | verifiedrevid = 464373213
| Watchedfields = changed
⚫ | verifiedrevid = 408784285
| IUPAC_name = (''RS'')-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide | IUPAC_name = (''RS'')-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide
| image = Oxiracetam.svg | image = Oxiracetam.svg
| width = 120px | width = 120px
| image2 = Oxiracetam3d.png | image2 = Oxiracetam.png
| width2 = 120px | width2 = 120px
| imagename = 1 : 1 mixture (racemate) | chirality = ]
| drug_name = Oxiracetam


<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename =
| pregnancy_category = | pregnancy_category =
| legal_AU = S4
| legal_status = Unscheduled (US) | legal_US = Unscheduled
| routes_of_administration = Oral | routes_of_administration = Oral


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability = 56-82%
| metabolism = | metabolism =
| elimination_half-life = 8 hours
| excretion = | excretion = Renal
| onset = 30-90 Minutes


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 62613-82-5 | CAS_number = 62613-82-5
| ATC_prefix = N06 | ATC_prefix = N06
Line 31: Line 34:
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4465 | ChemSpiderID = 4465
| UNII_Ref = {{fdacite|changed|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = P7U817352G | UNII = P7U817352G
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
Line 40: Line 43:
<!--Chemical data--> <!--Chemical data-->
| C=6 | H=10 | N=2 | O=3 | C=6 | H=10 | N=2 | O=3
| molecular_weight = 158.155
| smiles = O=C(N)CN1C(=O)CC(O)C1 | smiles = O=C(N)CN1C(=O)CC(O)C1
| InChI = 1/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10)
| InChIKey = IHLAQQPQKRMGSS-UHFFFAOYAL
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | 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) | StdInChI = 1S/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10)
Line 49: Line 49:
| StdInChIKey = IHLAQQPQKRMGSS-UHFFFAOYSA-N | StdInChIKey = IHLAQQPQKRMGSS-UHFFFAOYSA-N
}} }}
'''Oxiracetam''' is a ] drug of the ] family.<ref>{{cite journal | last1 = Malykh | first1 = AG | last2 = Sadaie | first2 = 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 | year = 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000}}</ref>


'''Oxiracetam''' (developmental code name '''ISF 2522''') is a ] drug of the ] family and a very mild ].<ref>{{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 }}</ref><ref>{{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 }}</ref> Several studies suggest that the substance is safe even when high doses are consumed for a long period of time.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref> However, the ] of the ] drug family is still a matter of research. Oxiracetam is not approved by ] for any medical use in the United States.
Several animal studies suggest that the substance is safe even when high doses are consumed for a long period of time. However, the ] of the ] drug family is still a matter of research.


==Clinical findings== ==Clinical findings==
There has been put effort into investigation the possible use of oxiracetam as a medication to attenuate the symptoms of dementia. <ref name="Gouliaev">Piracetam and other structurally related nootropics, Alex Haahr Gouliaeva, Alexander Senning, Brain Research Reviews Volume 19, Issue 2, May 1994, Pages 180-222, doi:10.1016/0165-0173(94)90011-6</ref> Oxiracetam has been studied to determine if it has an effect on symptoms of dementia,<ref name="Gouliaev">{{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 }}</ref> but no consistent results were obtained in patients with ] or organic solvent abuse.<ref name="Gouliaev"/>
However, no convincing results were obtained from studies where patients suffering from ] or organic solvent abuse were given 800 mg of the drug orally twice daily.<ref name="Gouliaev"/>


The proven effects of the drug are limited to beneficial effects that lead to higher scores in tests for logical performance, attention, concentration, memory and spatial orientation. These tests were performed on patients with mild to moderate dementia, and the doses were 800-2400 mg orally twice a day for one to six months. Improvement has also been seen in patients with exogenic post-concussion syndrome, organic brain syndromes and other dementias. According to V. Gallai ''et al'', oxiracetam is more effective than piracetam for this purpose.<ref name="Gouliaev"/> Patients with mild to moderate ] 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.<ref name="Gouliaev"/>

Oxiracetam-treated ] demonstrated a significant increase in spatial learning performance as determined by the ], compared to controls. This increase in performance was correlated to an increase in membrane-bound PKC.<ref>{{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 }}</ref>


==Pharmacokinetics== ==Pharmacokinetics==
Oxiracetam is well absorbed from the gastrointestinal tract with a bioavailability of 68-82% according to one source (E. Perucca ''et al'') and 56% according to another<ref name="Gouliaev"/>. Oxiracetam is well absorbed from the gastrointestinal tract with a bioavailability of 56-82%.<ref name="Gouliaev"/>
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 19-31 µg/ml at these doses. Peak serum levels are reached within one to three hours after a single 800&nbsp;mg or 2000&nbsp;mg oral dose, with the maximal serum concentration reaching between 19 and 31&nbsp;μg/ml at these doses.
⚫ Oxiracetam is mainly cleared renally and thus 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 ] with brain concentrations reaching 5.3% of that in the blood (measured one hour after a single 2000 mg intravenous dose)<ref name="Gouliaev"/>.
⚫ 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 concentrations of oxiracetam is found in the ], followed by the ], the ] and with the lowest concentrations in the striatum after a 200 mg/kg oral dose given to rats.<ref name="Gouliaev"/>


⚫ Oxiracetam is mainly cleared renally and approximately 84% is excreted unchanged in the urine.
==See also==
⚫ 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 ] with brain concentrations reaching 5.3% of those in the blood (measured one hour after a single 2000&nbsp;mg intravenous dose).<ref name="Gouliaev"/>


⚫ Clearance rates range from 9 to 95 ml/min and steady-state concentrations when 800&nbsp;mg is given twice daily range from 60 μM to 530 μM.
⚫ ==References==
{{reflist}}


⚫ The highest brain concentrations of oxiracetam are found in the ], followed by the ], the ] and with the lowest concentrations in the striatum after a 200&nbsp;mg/kg oral dose given to rats.<ref name="Gouliaev"/> Oxiracetam may be quantitated in plasma, serum or urine by liquid chromatography with one of several different detection techniques.<ref>{{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 }}</ref>
⚫ ==External links==
* James South,
*


The major metabolites of Oxiracetam include: beta-hydroxy-], N-aminoacetyl-], GABOB (beta-hydroxy-GABA) and ].{{Citation needed|date=May 2018}} Thus its metabolic route is exactly parallel to that of ], ], ], and all other members of the -racetam family, and also ].
{{Racetams}}
{{Psychostimulants, agents used for ADHD and nootropics}}


⚫ == References ==
⚫ ]
{{Reflist}}
⚫ ]
⚫ ]
⚫ ]
⚫ ]


⚫ == External links ==


*
{{nervous-system-drug-stub}}


== 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 = 237–41 | date = September 1992 | pmid = 1414239 | doi = 10.1111/j.1600-0404.1992.tb05077.x | s2cid = 9368980 | doi-access = free }}
* {{cite journal |last1=Li|first1=W |title=(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats |journal=Sci. Rep. |date=2017 |volume=7 |issue=1 |page=10052 |doi=10.1038/s41598-017-10283-4 |pmid=28855592 |pmc=5577264 |bibcode=2017NatSR...710052L |doi-access=free }}
* {{cite journal |last1=Villardita |first1=C|title=Clinical Studies with Oxiracetam in Patients with Dementia of Alzheimer Type and Multi-lnfarct Dementia of Mild to Moderate Degree |journal=Neuropsychobiology |date=1992 |volume=25 |issue=1|pages=24–28 |doi=10.1159/000118805 |pmid=1603291 }}
* {{cite journal |last1=Mondadori |first1=C |title=Effects of oxiracetam on learning and memory in animals: comparison with piracetam |journal=Clin. Neuropharmacol. |date=1986 |volume=9 |issue=Supp.3 |pages=S27-38 |doi=10.1097/00002826-198609003-00006 |pmid=3594453 |url=https://pubmed.ncbi.nlm.nih.gov/3594453/}}
* {{cite journal |last1=Hu |first1=S |title=Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude |journal=Brain and Behavior |date=2017 |volume=7 |issue=10 |pages=e00762 |doi=10.1002/brb3.762|pmid=29075554 |pmc=5651378 |doi-access=free }}
* {{cite journal |last1=Krylova |first1=N |title=A comparative study of the nootropic properties of piracetam and oxiracetam |journal=Farmakologiia I Toksikologiia |date=1991 |volume=54 |issue=1 |pages=14–6 |pmid=1860490 }}

{{refend}}

⚫ {{Racetams}}
{{Stimulants}}
{{Ionotropic glutamate receptor modulators}}

⚫ ]
⚫ ]
]
⚫ ]
⚫ ]
⚫ ]

Latest revision as of 22:02, 27 September 2024

Chemical compound

Pharmaceutical compound
Oxiracetam
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Unscheduled
Pharmacokinetic data
Bioavailability56-82%
Onset of action30-90 Minutes
Elimination half-life8 hours
ExcretionRenal
Identifiers
IUPAC name
  • (RS)-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.164.173 Edit this at Wikidata
Chemical and physical data
FormulaC6H10N2O3
Molar mass158.157 g·mol
3D model (JSmol)
ChiralityRacemic mixture
SMILES
  • O=C(N)CN1C(=O)CC(O)C1
InChI
  • InChI=1S/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10)
  • Key:IHLAQQPQKRMGSS-UHFFFAOYSA-N
  (what is this?)  (verify)

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 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, 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.

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.

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.

The major metabolites of Oxiracetam include: beta-hydroxy-2-pyrrolidone, N-aminoacetyl-GABOB, GABOB (beta-hydroxy-GABA) and glycine. 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

  1. Malykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767. S2CID 12176745.
  2. Valzelli L, Baiguerra G, Giraud O (June 1986). "Difference in learning and retention by Albino Swiss mice. Part III. Effect of some brain stimulants". Methods and Findings in Experimental and Clinical Pharmacology. 8 (6): 337–41. PMID 3736279.
  3. Parnetti L, Mecocci P, Petrini A, Longo A, Buccolieri A, Senin U (1989). "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". Neuropsychobiology. 22 (2): 97–100. doi:10.1159/000118599. PMID 2518332.
  4. Itil TM, Menon GN, Songar A, Itil KZ (1986). "CNS pharmacology and clinical therapeutic effects of oxiracetam". Clinical Neuropharmacology. 9 (Suppl 3): S70-2. doi:10.1097/00002826-198609003-00011. PMID 3594458.
  5. Perucca E, Parini J, Albrici A, Visconti M, Ferrero E (1987). "Oxiracetam pharmacokinetics following single and multiple dose administration in the elderly". European Journal of Drug Metabolism and Pharmacokinetics. 12 (2): 145–8. doi:10.1007/bf03189889. PMID 3691580. S2CID 11415210.
  6. ^ Gouliaev AH, Senning A (May 1994). "Piracetam and other structurally related nootropics". Brain Research. Brain Research Reviews. 19 (2): 180–222. doi:10.1016/0165-0173(94)90011-6. PMID 8061686. S2CID 18122566.
  7. Fordyce DE, Clark VJ, Paylor R, Wehner JM (February 1995). "Enhancement of hippocampally-mediated learning and protein kinase C activity by oxiracetam in learning-impaired DBA/2 mice". Brain Research. 672 (1–2): 170–6. doi:10.1016/0006-8993(94)01389-y. PMID 7749739. S2CID 13191058.
  8. Baselt R (2014). Disposition of Toxic Drugs and Chemicals in Man (10th ed.). Seal Beach, CA: Biomedical Publications. pp. 1524–1525.

External links

Further reading

Racetams
Racetams
Phenylpiracetams
Racetam-like
Stimulants
Adamantanes
Adenosine antagonists
Alkylamines
Ampakines
Arylcyclohexylamines
Benzazepines
Cathinones
Cholinergics
Convulsants
Eugeroics
Oxazolines
Phenethylamines
Phenylmorpholines
Piperazines
Piperidines
Pyrrolidines
Racetams
Tropanes
Tryptamines
Others
ATC code: N06B
Ionotropic glutamate receptor modulators
AMPARTooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
KARTooltip Kainate receptor
NMDARTooltip N-Methyl-D-aspartate receptor
Categories: