oxiracetam
Older mixed-dementia and scopolamine-challenge studies reported improvements on selected cognitive measures. In a 500-person, 36-week post-stroke trial, oxiracetam did not improve either primary cognitive outcome, and no study tested enhancement in healthy, unimpaired people.
Small-molecule racetam
- OVERCOME randomized 500 chronic stroke survivors; MMSE and CDR-SB changes were both null.
- A 60-person 1992 mixed-dementia trial reported several favorable tests without usable effect sizes or multiplicity detail.
- A 12-person scopolamine challenge found delayed-recall rescue at 1,600 mg; everyone was pharmacologically impaired.
- LOCATE’s positive result belongs to IV L-oxiracetam, and it did not test racemic oxiracetam against placebo.
What is ordinary oxiracetam?
Ordinary oxiracetam is a racemic mixture of R and S enantiomers. L-oxiracetam is the isolated S enantiomer and has separate evidence.
Studies used oral 800 mg twice daily in dementia and post-stroke cohorts, acute 800 to 2,400 mg doses during scopolamine challenge, and IV 6 g/day racemate during acute TBI. Those routes and populations are not interchangeable.
PubChem: oxiracetam chemical identity
Government chemical identity database
National Library of Medicine. PubChem CID 4626.
C6H10N2O3; molecular weight 158.16 g/mol.
- Participants / model
- Chemical record
- Follow-up
- Living database
- Study design
- Curated structure record
Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.
Read the original sourceClinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree.
Primary human study
Villardita C et al. Neuropsychobiology. 1992. PMID 1603291. DOI 10.1159/000118805.
Several cognitive tests favored oxiracetam after a 90-day randomized phase; the later extension was open-label.
- Participants / model
- 60 people with Alzheimer-type or multi-infarct dementia
- Follow-up
- 90 days; extension up to 1 year
- Study design
- Randomized double-blind placebo comparison followed by uncontrolled extension
The extension cannot preserve the randomized causal comparison. Multiple tests and a small mixed-dementia cohort limit inference.
Read the original sourceOxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial.
Randomized controlled trial
Lim JS et al. European Stroke Journal. 2026. PMID 41614470; related indexed record PMID 40882961. DOI 10.1093/esj/23969873251350141.
No significant between-group change in MMSE or CDR-SB over 36 weeks; 500 randomized and 457 had the analyzed endpoint data.
- Participants / model
- 500 randomized; 457 with complete cognitive outcomes; 496 in the reported safety analysis
- Follow-up
- 36 weeks
- Study design
- Multicenter double-blind placebo-controlled trial
- Funding
- Korean Drug Company funded the trial; authors state it had no role in design, conduct, analysis or submission.
Modified intention-to-treat analysis excluded missing week-36 cognitive outcomes without imputation. Both groups remained relatively stable; baseline MMSE was high. Physical activity was not randomized and the treatment-by-activity interaction was nonsignificant (p=0.76). The text gives inconsistent accounting of treated participants; safety denominators come from Table 3.
Read the original sourceEfficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R. Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceWhat happened in the modern post-stroke trial?
Oxiracetam did not outperform placebo on either primary cognitive measure after 36 weeks.
OVERCOME randomized 500 adults a median 32 months after stroke. The efficacy analysis included 457 with week-36 data: 226 oxiracetam and 231 placebo. Missing final scores were excluded rather than imputed.
MMSE changed +0.13 versus +0.27 points (p=0.49). CDR-Sum of Boxes changed −0.14 versus −0.08 (p=0.38). Exploratory imaging and subgroup patterns came after those clinical endpoints failed.
Oxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial.
Randomized controlled trial
Lim JS et al. European Stroke Journal. 2026. PMID 41614470; related indexed record PMID 40882961. DOI 10.1093/esj/23969873251350141.
No significant between-group change in MMSE or CDR-SB over 36 weeks; 500 randomized and 457 had the analyzed endpoint data.
- Participants / model
- 500 randomized; 457 with complete cognitive outcomes; 496 in the reported safety analysis
- Follow-up
- 36 weeks
- Study design
- Multicenter double-blind placebo-controlled trial
- Funding
- Korean Drug Company funded the trial; authors state it had no role in design, conduct, analysis or submission.
Modified intention-to-treat analysis excluded missing week-36 cognitive outcomes without imputation. Both groups remained relatively stable; baseline MMSE was high. Physical activity was not randomized and the treatment-by-activity interaction was nonsignificant (p=0.76). The text gives inconsistent accounting of treated participants; safety denominators come from Table 3.
Read the original sourceWhy did the 1992 dementia study look more positive?
It randomized only 60 people with Alzheimer-type or multi-infarct dementia for 90 days and reported advantages across several tests.
The abstract gives no treatment effect sizes or multiplicity handling. Twenty-nine treated participants entered an uncontrolled extension, where practice, selective continuation and natural change cannot be separated from treatment.
Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree.
Primary human study
Villardita C et al. Neuropsychobiology. 1992. PMID 1603291. DOI 10.1159/000118805.
Several cognitive tests favored oxiracetam after a 90-day randomized phase; the later extension was open-label.
- Participants / model
- 60 people with Alzheimer-type or multi-infarct dementia
- Follow-up
- 90 days; extension up to 1 year
- Study design
- Randomized double-blind placebo comparison followed by uncontrolled extension
The extension cannot preserve the randomized causal comparison. Multiple tests and a small mixed-dementia cohort limit inference.
Read the original sourceWas oxiracetam tested in healthy volunteers?
Yes, but only after researchers induced amnesia with scopolamine. In 12 volunteers, the 1,600 mg condition improved delayed word recall versus placebo.
Every relevant session included 0.5 mg subcutaneous scopolamine. The study had three active doses and four experimental groups, with no unchallenged oxiracetam-versus-placebo condition. It shows possible rescue, not better-than-normal memory.
Effects of acute doses of oxiracetam in the scopolamine model of human amnesia.
Primary human challenge study
Preda L et al. Psychopharmacology. 1993. PMID 7870912.
Among 12 healthy volunteers given scopolamine, 1,600 mg oxiracetam improved delayed word-list recall; no unchallenged drug-versus-placebo condition tested normal enhancement.
- Participants / model
- 12 healthy volunteers after experimentally induced scopolamine amnesia
- Follow-up
- Acute sessions
- Study design
- Incomplete randomized crossover dose challenge
Four experimental groups and three active doses make the study very small; this is induced-deficit rescue.
Read the original sourceDo scan or AMPA-receptor findings overturn the clinical result?
No. OVERCOME’s imaging patterns were exploratory, and a 2026 AMPA-receptor paper used a laboratory Alzheimer model rather than patients.
The 2026 AMPA-receptor result is preclinical. OVERCOME's exploratory imaging patterns did not correspond to improvement on its primary cognitive outcomes.
Oxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial.
Randomized controlled trial
Lim JS et al. European Stroke Journal. 2026. PMID 41614470; related indexed record PMID 40882961. DOI 10.1093/esj/23969873251350141.
No significant between-group change in MMSE or CDR-SB over 36 weeks; 500 randomized and 457 had the analyzed endpoint data.
- Participants / model
- 500 randomized; 457 with complete cognitive outcomes; 496 in the reported safety analysis
- Follow-up
- 36 weeks
- Study design
- Multicenter double-blind placebo-controlled trial
- Funding
- Korean Drug Company funded the trial; authors state it had no role in design, conduct, analysis or submission.
Modified intention-to-treat analysis excluded missing week-36 cognitive outcomes without imputation. Both groups remained relatively stable; baseline MMSE was high. Physical activity was not randomized and the treatment-by-activity interaction was nonsignificant (p=0.76). The text gives inconsistent accounting of treated participants; safety denominators come from Table 3.
Read the original sourceOxiracetam Improves Cognitive Disorder in AD by Modulating AMPAR Subunits GluA1/GluA2 Kinetics.
Preclinical primary study
Guo S et al. Cell Biochemistry and Biophysics. 2026. PMID 41739317.
Oxiracetam altered AMPA-receptor-subunit kinetics and selected outcomes in a laboratory Alzheimer model.
- Participants / model
- Laboratory Alzheimer-disease model
- Follow-up
- Experimental treatment period
- Study design
- Preclinical mechanistic experiments
The study used a laboratory Alzheimer model and did not test cognition, prevention, or longevity in people.
Read the original sourceWhat did LOCATE show about the racemate?
LOCATE found a day-90 LOTCA benefit for IV L-oxiracetam versus placebo. It did not report a prespecified racemic-oxiracetam-versus-placebo efficacy estimate.
The printed racemate mean improved from baseline, but placebo improved too. L-oxiracetam exceeded racemate by 4.54 points. The S-enantiomer result cannot be assigned to ordinary oxiracetam.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R. Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceWhat about the 423-person Chinese dementia report?
It combined blinded and open cohorts and found no significant difference between domestic oxiracetam and piracetam over 60 days.
There was no placebo, so the active comparison cannot establish that either drug worked. The abstract’s response counts do not reconcile with its stated total, making the response rate reported in the abstract unusable.
Chinese active-comparator and open study, 1997
Primary human clinical report
Zhao GP et al. Chinese Journal of Clinical Pharmacology. 1997;(1):18 to 22.
The report found no statistically significant difference between oxiracetam and piracetam; it combined blinded and open cohorts.
- Participants / model
- 423 reported patients with dementia across controlled and open cohorts
- Follow-up
- 60 days
- Study design
- Randomized double-blind active-comparator component plus open treatment
The abstract’s response counts and percentages do not reconcile with its stated 327 treated total. Exact efficacy-set denominators and the claimed response rate are therefore not used. Nonsignificance is not proof of equivalence.
Read the original sourceWhat did the larger trials report about harm?
In OVERCOME, adverse events occurred in 100/244 oxiracetam and 88/252 placebo recipients; serious events occurred in 21/244 and 16/252. Neither difference was significant.
LOCATE reported treatment-related events in 41/236 racemate, 22/235 L-oxiracetam and 11/119 placebo recipients (overall p=0.049) during 14 days of IV treatment.
These data cover defined pharmaceutical products and limited durations. They do not settle chronic healthy use, pregnancy, stacks, kidney impairment or retail-product identity.
Oxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial.
Randomized controlled trial
Lim JS et al. European Stroke Journal. 2026. PMID 41614470; related indexed record PMID 40882961. DOI 10.1093/esj/23969873251350141.
No significant between-group change in MMSE or CDR-SB over 36 weeks; 500 randomized and 457 had the analyzed endpoint data.
- Participants / model
- 500 randomized; 457 with complete cognitive outcomes; 496 in the reported safety analysis
- Follow-up
- 36 weeks
- Study design
- Multicenter double-blind placebo-controlled trial
- Funding
- Korean Drug Company funded the trial; authors state it had no role in design, conduct, analysis or submission.
Modified intention-to-treat analysis excluded missing week-36 cognitive outcomes without imputation. Both groups remained relatively stable; baseline MMSE was high. Physical activity was not randomized and the treatment-by-activity interaction was nonsignificant (p=0.76). The text gives inconsistent accounting of treated participants; safety denominators come from Table 3.
Read the original sourceEfficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R. Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceStudies and sources
Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree.
Primary human study
Villardita C et al. Neuropsychobiology. 1992. PMID 1603291. DOI 10.1159/000118805.
Several cognitive tests favored oxiracetam after a 90-day randomized phase; the later extension was open-label.
- Participants / model
- 60 people with Alzheimer-type or multi-infarct dementia
- Follow-up
- 90 days; extension up to 1 year
- Study design
- Randomized double-blind placebo comparison followed by uncontrolled extension
The extension cannot preserve the randomized causal comparison. Multiple tests and a small mixed-dementia cohort limit inference.
Read the original sourceOxiracetam and physical activity in preventing cognitive decline after stroke: A multicenter, randomized controlled trial.
Randomized controlled trial
Lim JS et al. European Stroke Journal. 2026. PMID 41614470; related indexed record PMID 40882961. DOI 10.1093/esj/23969873251350141.
No significant between-group change in MMSE or CDR-SB over 36 weeks; 500 randomized and 457 had the analyzed endpoint data.
- Participants / model
- 500 randomized; 457 with complete cognitive outcomes; 496 in the reported safety analysis
- Follow-up
- 36 weeks
- Study design
- Multicenter double-blind placebo-controlled trial
- Funding
- Korean Drug Company funded the trial; authors state it had no role in design, conduct, analysis or submission.
Modified intention-to-treat analysis excluded missing week-36 cognitive outcomes without imputation. Both groups remained relatively stable; baseline MMSE was high. Physical activity was not randomized and the treatment-by-activity interaction was nonsignificant (p=0.76). The text gives inconsistent accounting of treated participants; safety denominators come from Table 3.
Read the original sourcePubChem: oxiracetam chemical identity
Government chemical identity database
National Library of Medicine. PubChem CID 4626.
C6H10N2O3; molecular weight 158.16 g/mol.
- Participants / model
- Chemical record
- Follow-up
- Living database
- Study design
- Curated structure record
Formula and molecular weight establish the recorded structure, not the contents of a retail product or an effective dose.
Read the original sourceEfficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R. Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceChinese active-comparator and open study, 1997
Primary human clinical report
Zhao GP et al. Chinese Journal of Clinical Pharmacology. 1997;(1):18 to 22.
The report found no statistically significant difference between oxiracetam and piracetam; it combined blinded and open cohorts.
- Participants / model
- 423 reported patients with dementia across controlled and open cohorts
- Follow-up
- 60 days
- Study design
- Randomized double-blind active-comparator component plus open treatment
The abstract’s response counts and percentages do not reconcile with its stated 327 treated total. Exact efficacy-set denominators and the claimed response rate are therefore not used. Nonsignificance is not proof of equivalence.
Read the original sourceEffects of acute doses of oxiracetam in the scopolamine model of human amnesia.
Primary human challenge study
Preda L et al. Psychopharmacology. 1993. PMID 7870912.
Among 12 healthy volunteers given scopolamine, 1,600 mg oxiracetam improved delayed word-list recall; no unchallenged drug-versus-placebo condition tested normal enhancement.
- Participants / model
- 12 healthy volunteers after experimentally induced scopolamine amnesia
- Follow-up
- Acute sessions
- Study design
- Incomplete randomized crossover dose challenge
Four experimental groups and three active doses make the study very small; this is induced-deficit rescue.
Read the original sourceOxiracetam Improves Cognitive Disorder in AD by Modulating AMPAR Subunits GluA1/GluA2 Kinetics.
Preclinical primary study
Guo S et al. Cell Biochemistry and Biophysics. 2026. PMID 41739317.
Oxiracetam altered AMPA-receptor-subunit kinetics and selected outcomes in a laboratory Alzheimer model.
- Participants / model
- Laboratory Alzheimer-disease model
- Follow-up
- Experimental treatment period
- Study design
- Preclinical mechanistic experiments
The study used a laboratory Alzheimer model and did not test cognition, prevention, or longevity in people.
Read the original sourceWhy is oxiracetam in D tier?
D reflects the strongest modern test: 36 weeks of oral oxiracetam did not improve either primary cognitive outcome in 500 post-stroke participants. Older disease and induced-impairment signals do not establish healthy cognition, prevention or longevity.