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.
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 56-82% |
| Onset of action | 30-90 Minutes |
| Elimination half-life | 8 hours |
| Excretion | Renal |
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| ECHA InfoCard | 100.164.173 |
| Chemical and physical data | |
| Formula | C6H10N2O3 |
| Molar mass | 158.157 g·mol−1 |
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| Chirality | Racemic mixture |
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Clinical findings
editOxiracetam has been studied to determine if it has an effect on symptoms of dementia,[6] but no consistent results were obtained in patients with Alzheimer's dementia or organic solvent abuse.[6]
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.[6]
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.[7]
Pharmacokinetics
editOxiracetam 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.
References
edit- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b c d e f 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.
- ^ 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.
- ^ Baselt R (2014). Disposition of Toxic Drugs and Chemicals in Man (10th ed.). Seal Beach, CA: Biomedical Publications. pp. 1524–1525.
External links
editFurther reading
edit- Bottini G, Vallar G, Cappa S, Monza GC, Scarpini E, Baron P, et al. (September 1992). "Oxiracetam in dementia: a double-blind, placebo-controlled study". Acta Neurologica Scandinavica. 86 (3): 237–41. doi:10.1111/j.1600-0404.1992.tb05077.x. PMID 1414239. S2CID 9368980.
- Li W (2017). "(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats". Sci. Rep. 7 (1): 10052. Bibcode:2017NatSR...710052L. doi:10.1038/s41598-017-10283-4. PMC 5577264. PMID 28855592.
- Villardita C (1992). "Clinical Studies with Oxiracetam in Patients with Dementia of Alzheimer Type and Multi-lnfarct Dementia of Mild to Moderate Degree". Neuropsychobiology. 25 (1): 24–28. doi:10.1159/000118805. PMID 1603291.
- Mondadori C (1986). "Effects of oxiracetam on learning and memory in animals: comparison with piracetam". Clin. Neuropharmacol. 9 (Supp.3): S27-38. doi:10.1097/00002826-198609003-00006. PMID 3594453.
- Hu S (2017). "Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude". Brain and Behavior. 7 (10): e00762. doi:10.1002/brb3.762. PMC 5651378. PMID 29075554.
- Krylova N (1991). "A comparative study of the nootropic properties of piracetam and oxiracetam". Farmakologiia I Toksikologiia. 54 (1): 14–6. PMID 1860490.