Oxiracetam

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Oxiracetam
Oxiracetam.svg
Oxiracetam.png
Clinical data
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US:Unscheduled
Pharmacokinetic data
Bioavailability 56-82%
Onset of action 30-90 Minutes
Elimination half-life 8 hours
Excretion Renal
Identifiers
  • (RS)-2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.164.173 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C6H10N2O3
Molar mass 158.157 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • O=C(N)CN1C(=O)CC(O)C1
  • InChI=1S/C6H10N2O3/c7-5(10)3-8-2-4(9)1-6(8)11/h4,9H,1-3H2,(H2,7,10) Yes check.svgY
  • Key:IHLAQQPQKRMGSS-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Oxiracetam (developmental code name ISF 2522) is a nootropic drug of the racetam family and a very mild stimulant. [1] [2] Several studies suggest that the substance is safe even when high doses are consumed for a long period of time. [3] [4] [5] 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.

Contents

Clinical findings

There has been effort put into investigating the possible use of oxiracetam as a medication to attenuate the symptoms of dementia. [6] However, no convincing results were obtained from studies of patients with Alzheimer's dementia or organic solvent abuse. [6]

Tests performed on patients with mild to moderate dementia experienced 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. [6]

Oxiracetam-treated DBA 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. [7]

Pharmacokinetics

Oxiracetam is well absorbed from the gastrointestinal tract with a bioavailability of 56-82%. [6] 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). [6]

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. [6] Oxiracetam may be quantitated in plasma, serum or urine by liquid chromatography with one of several different detection techniques. [8]

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

Related Research Articles

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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. 1 2 3 4 5 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.

Further reading