Effects Of Piracetam Research Articles

Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells

Breath-holding spells (BHS) are apparently frightening events occurring in otherwise healthy children.The aim of this study was to evaluate the efficacy of piracetam in the treatment of breath-holding spells. Forty patients with BHS (who were classified into two groups)were involved in a double-blinded placebo-controlled prospective study. Piracetam was given to group A while group B received placebo. Patients were followed monthly for a total period of 4 months. The numbers of attacks/month before and monthly after treatment were documented, and the overall number of attacks/month after treatment was calculated in both groups. The median number of attacks/month before treatment in the two groups was 5.5 and 5,respectively, while after the first month of treatment, it was 2 and 5, respectively. The median overall number of attacks/month after treatment in both groups was 1 and 5, respectively.There was a significant decline of number of attacks after piracetam treatment compared to placebo (p value<0.001). There were no reported side effects of the piracetam throughout the study period. In conclusion, piracetam is a safe and effective drug for the treatment of breath-holding spells in children.

Effects of piracetam on pediatric breath holding spells: a randomized double blind controlled trial.

Breath holding spells (BHS) are common paroxysmal non-epileptic events in the pediatric population which are very stressfull despite their harmless nature. There has been no specific treatment found for the spells yet. The aim of this study was to evaluate the efficacy of piracetam (2-oxo-l-pyrrolidine) on these children. In this randomized double blind clinical trial study, 150 children with severe BHS referred to our pediatric outpatient service were enrolled from August 2011 to July 2012. The patients were randomized into two equal groups. One received 40mg/kg/day piracetam and the other group received placebo, twice daily. Patients were followed monthly for three months. The number of attacks/month before and after treatment were documented. Of the enrolled patients, 86 were boys. The mean age of the patients was 17 months (range, 6 to 24 months). In the piracetam group, 1 month after treatment an 81% response to treatment was found. In the placebo group, none of the patients had complete remission and 7% of the cases had partial remission. Overall, control of breath-holding spells was observed in 91% of the patients in the group taking piracetam as compared with 16% in the group taking placebo at the end of the study. There was no significant difference detected between the groups regarding the prevalence of drug side effects. A significant difference was detected between piracetam and placebo in prevention and controlling BHS. Piracetam (40mg/kg/day) had a good effect on our patients.

A study to evaluate the effect of nootropic drug—Piracetam on DNA damage in leukocytes and macrophages

Piracetam is a nootropic drug that protects neurons in neuropathological and age-related diseases and the activation and modulation of peripheral blood cells in patients with neuropathological conditions is well known. Therefore, in the present study, in vivo, ex vivo, and in vitro tests were conducted to investigate the effect of piracetam on leukocytes and macrophages. Lipopolysaccharide (LPS) causes oxidative DNA damage; thus, in the present study, LPS was used as a tool to induce DNA damage. In vivo experiments were conducted on Sprague Dawley rats, and piracetam (600 mg/kg, oral) was provided for five consecutive days. On the fifth day, a single injection of LPS (10 mg/kg, i.p.) was administered. Three hours after LPS injection, blood leukocytes and peritoneal macrophages were collected and processed, and a variety of different assays were conducted. Ex vivo treatments were performed on isolated rat blood leukocytes, and in vitro experiments were conducted on rat macrophage cell line J774A.1. Cell viability and the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and DNA damage were estimated in untreated (control) and piracetam-, LPS- and LPS + piracetam-treated leukocytes and macrophages. In vivo experiments revealed that rats pretreated with piracetam were significantly protected against LPS-induced increases in ROS levels and DNA damage. Ex vivo isolated leukocytes and J774A.1 cells treated with LPS exhibited augmented ROS levels and DNA damage, which were attenuated with piracetam treatment. Thus, the present study revealed the salutary effect of piracetam against LPS-induced oxidative stress and DNA damage in leukocytes and macrophages.

Oxidative stress in a model of toxic demyelination in rat brain: The effect of piracetam and vinpocetine

Oxidative stress in a model of toxic demyelination in rat brain: The effect of piracetam and vinpocetine

Effect of Systemic Piracetam Treatment on Flap Survival and Vascular Endothelial Growth Factor Expression after Ischemia-Reperfusion Injury

The effects of piracetam on flap survival, ischemia-reperfusion (I/R) injury, and vascular endothelial growth factor (VEGF) expression were evaluated in this study. Unipedicled epigastric flap model was used in 36 rats and was evaluated within 4 groups. The flap was elevated and untreated in Group 1. Postoperative piracetam treatment was given for 7 days in Group 2. In Group 3, 4 hours of ischemia and 2 hours of reperfusion were applied. I/R was applied to Group 4 and piracetam was given 30 minutes before reperfusion and postoperatively for 7 days. Laser Doppler flowmetry was used to measure blood flow changes. VEGF expression was determined using immunohistochemical methods on tissue samples taken after the completion of 2 hours reperfusion in groups 3 and 4. Flap necrosis was measured on the day 7 in all groups. Blood flow rates did not show significant difference between piracetam treated and untreated I/R groups. Piracetam significantly reduced necrosis area both in ischemic and nonischemic flaps ( P < 0.05). VEGF expression was significantly increased in piracetam-treated Group 4 compared with Group 3 ( P = 0.005). This experimental study demonstrates that systemic piracetam treatment improves survival of pedicled flaps, reduces necrosis amounts, and increases VEGF expression in I/R induced flaps.

Oxidative Stress in a Model of Toxic Demyelination in Rat Brain: The Effect of Piracetam and Vinpocetine

We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

Effects of piracetam on behavior and memory in adult zebrafish

Piracetam, a derivative of γ-aminobutyric acid, exerts memory-enhancing and mild anxiolytic effects in human and rodent studies. To examine the drug's behavioral profile further, we assessed its effects on behavioral and endocrine (cortisol) responses of adult zebrafish ( Danio rerio) – a novel model species rapidly gaining popularity in neurobehavioral research. Overall, acute piracetam did not affect zebrafish novel tank and light–dark box behavior at mild doses (25–400 mg/L), but produced nonspecific behavioral inhibition at 700 mg/L. No effects on cortisol levels or inter-/intra-session habituation in the novel tank test were observed for acute or chronic mild non-sedative dose of 200 mg/L. In contrast, fish exposed to chronic piracetam at this dose performed significantly better in the cued learning plus-maze test. This observation parallels clinical and rodent literature on the behavioral profile of piracetam, supporting the utility of zebrafish paradigms for testing nootropic agents.

Cerebroprotective Effect of Piracetam in Patients Undergoing Open Heart Surgery

Reduction of cognitive function is a possible side effect after the use of cardiopulmonary bypass (CPB) during cardiac surgery. Since it has been proven that piracetam is cerebroprotective in patients undergoing coronary bypass surgery, we investigated the effects of piracetam on the cognitive performance of patients undergoing open heart surgery. Patients scheduled for elective open heart surgery were randomized to the piracetam or placebo group in a double-blind study. Patients received 12 g of piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on day 3, postoperatively. To assess the overall cognitive function and the degree of cognitive decline across all tests after the surgery, we combined the six test-scores by principal component analysis. A total of 88 patients with a mean age of 67 years were enrolled into the study. The mean duration of CPB was 110 minutes. Preoperative clinical parameters and overall cognitive functions were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed deterioration of cognitive function in both groups (piracetam: preoperative 0.19 ± 0.97 vs. postoperative -0.97 ± 1.38, p <0.0005 and placebo: preoperative -0.14 ± 0.98 vs. postoperative -1.35 ± 1.23, p <0.0005). Patients taking piracetam did not perform better than those taking placebo, and both groups had the same decline of overall cognitive function (p = 0.955). Piracetam had no cerebroprotective effect in patients undergoing open heart surgery. Unlike the patients who underwent coronary surgery, piracetam did not reduce the early postoperative decline of neuropsychological abilities in heart valve patients.

Preventive effect of Piracetam and Vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture

The present study investigates the potential of Piracetam and Vinpocetine (nootropic drugs, known to possess neuroprotective properties) in preventing hypoxia-reoxygenation induced oxidative stress in primary hippocampal cell culture. The hippocampal culture was exposed to hypoxia (95% N 2, 5% CO 2) for 3 h and followed by 1 h of reoxygenation (21% O 2 and 5% CO 2) at 37 °C. The primary hippocampal cultures were supplemented with the optimum dose of Piracetam and Vinpocetine, independently, and the cultures were divided into six groups, viz. Control/Normoxia, Hypoxia, Hypoxia + Piracetam, Hypoxia + Vinpocetine, Normoxia + Piracetam and Normoxia + Vinpocetine. The cell-viability assays and biochemical oxidative stress parameters were evaluated for each of the six groups. Administration of 1 mM Piracetam or 500 nM Vinpocetine significantly prevents the culture from hypoxia-reoxygenation injury when determined by Neutral Red assay, LDH release and Acetylcholine esterase activity. Results showed that Piracetam and Vinpocetine supplementation significantly prevented the fall of mitochondrial membrane potential, rise in ROS generation and reduction in antioxidant levels associated with the hypoxia-reoxygenation injury. In conclusion, the present study establishes that both Piracetam and Vinpocetine give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal cell culture.

The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ß‐amyloid peptide

beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

Improved mitochondrial function in brain aging and Alzheimer disease - the new mechanism of action of the old metabolic enhancer piracetam

Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions.

The Effect Of Piracetam On Liver Damage In Dogs Submitted To Hemorrhagic Shock

Background: To investigate the effect of piracetam on liver damage in dogs submitted to hemorrhagic shock. Methods: The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was caused in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was caused and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment at 60, 120 and 180 minutes for lactate, arterial blood gases, bicarbonate, aspartate transaminase and alanine transaminase analysis. For histopathological examination, liver tissue samples were obtained at the end of the experiment.Results: It was observed that the improvement in lactate, aspartate transaminase and alanine transaminase levels in Group III was more than Group II. It was seen that the recovery in liver damage in Group III was greater than control group. Conclusion: Piracetam, added to the treatment, may decrease liver damage in hemorrhagic shock.

Habituation of caddies Chaetopteryx villosa Fabr. Larvae to vibrational stimulus and effect of piracetam on it

Habituation to a vibrational stimulus was studied in intact caddies Chaetopteryx villosa Fabr. of the last age before pupation and of the larvae placed for 72 h into pyracetam solution (100 mg/l). The vibrational stimulus was shown to produce a passive-defensive reaction: the caddies were pulled into the house and stood still. In the course of the experiment the time of stay in the house decreased statistically significantly in both groups. Pyracetam did not affect the defensive reaction at the initial moment of the first vibrational stimulus, so both in the experimental and in the control groups the number of contracted larvae was equal and all of them remained in the house for the first seconds of vibration. However, the compound increased the number of larvae that did not respond to the next vibrational stimulus and decreased the number of larvae that remain in the house throughout all 10 s of action by accelerating on the whole the habituation. Hence, on this model, the mnemotropic effect of the standard nootrope has been realized, which earlier was established by other methods in mammals, the lower vertebrates, and the higher invertebrates. This indicates that this model also is perspective for comparative studies of effect of nootropic substances on the higher nervous activity.

A Systematic Review and Meta-Analysis of the Efficacy of Piracetam and Piracetam-Like Compounds in Experimental Stroke

Background/Objective: Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. Methods: We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Results: Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1–44.4). The median study quality was 4/10 (inter-quartile range = 4–6). Conclusion: Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias.

Piracetam improves cognitive deficits caused by chronic cerebral hypoperfusion in rats.

Piracetam is the derivate of gamma-aminobutyric acid, which improves the cognition,memory,consciousness, and is widely applied in the clinical treatment of brain dysfunction. In the present experiments, we study the effects of piracetam on chronic cerebral hypoperfused rats and observe its influence on amino acids, synaptic plasticity in the Perforant path-CA3 pathway and apoptosis in vivo. Cerebral hypoperfusion for 30 days by occlusion of bilateral common carotid arteries induced marked amnesic effects along with neuron damage, including: (1) spatial learning and memory deficits shown by longer escape latency and shorter time spent in the target quadrant; (2) significant neuronal loss and nuclei condensation in the cortex and hippocampus especially in CA1 region; (3) lower induction rate of long term potentiation, overexpression of BAX and P53 protein, and lower content of excitatory and inhibitory amino acids in hippocampus. Oral administration of piracetam (600 mg/kg, once per day for 30 days) markedly improved the memory impairment, increased the amino acid content in hippocampus, and attenuated neuronal damage. The ability of piracetam to attenuate memory deficits and neuronal damage after hypoperfusion may be beneficial in cerebrovascular type dementia.

Piracetam Prevents Cognitive Decline in Coronary Artery Bypass: A Randomized Trial Versus Placebo

Coronary artery bypass grafting (CABG) can be associated with postoperative cognitive impairment and ischemic stroke. No effective treatment is currently available. The aim of this study was to evaluate the effectiveness of piracetam to treat the cognitive impairment after CABG in an investigator-initiated, double-blind, placebo-controlled, randomized clinical trial. Patients undergoing CABG (n = 98) were randomized to placebo (n = 48) or piracetam (n = 50). Study drugs were administered intravenously (150 mg/kg daily; 300 mg/kg on the day of surgery) from the day before surgery to 6 days after surgery, then orally (12 g/day) up to 6 weeks after surgery. Cognitive function was assessed before surgery (baseline) and 6 weeks after surgery (outcome) by using a battery of 12 neuropsychologic tests. The Spielberger Anxiety Inventory and the Beck Depression Inventory were also administered. The combined score derived from the standardized neuropsychologic assessments was analyzed by using an analysis of covariance with baseline and education as covariates. Six weeks after surgery, the combined score indicated a statistically significant treatment effect in the per protocol population (1.848, p = 0.041) and a tendency towards statistical significance in the intent-to-treat population (1.624, p = 0.064) in the group treated with piracetam, but no statistically significant treatment effect was seen in the placebo. The state of anxiety measured by the Spielberger Anxiety Inventory was decreased in both groups (-9.27 and -6.37 in the placebo and piracetam groups, respectively). Six weeks after CABG, cognition was significantly improved in patients treated with piracetam. Additional trials are required to confirm these effects.

Piracetam for Acute Ischemic Stroke

Piracetam is a drug which has been marketed in several countries for many years as a “nootropic” agent (that is, a drug which has metabolic activity on human brain), and for the treatment of myoclonus. Recently, a Cochrane review has been published on efficacy of piracetam on ameliorating language in aphasic stroke patients; the drug has been reconsidered for acute stroke treatment as well. The objective of this review was to assess the effects of piracetam in acute presumed ischemic stroke. Randomized trials comparing piracetam with control, with at least mortality reported and entry to the trial within ≈48 hours of stroke onset. Two reviewers (S.R., M.G.C.) extracted data and assessed trial quality, and this was checked by the other 2 …

Piracetam: its possible mode of action in children with learning disabilities and its effect on in vitro cell growth

The use of pharmaceutical products such as Piracetam (Nootropil®) for the treatment of learning disabilities is becoming increasingly prevalent, and some studies have shown successful treatment of learning disabilities in children. This research article will discuss traditional uses of Piracetam, as well as uses in learning disabilities, with particular focus on case studies where it has been given to children with learning disabilities. Furthermore, we investigate how Piracetam could potentially enhance learning, with specific focus on brain areas. However, even though Piracetam may enhance learning, the question that arises is how safe it is at a cellular level. Therefore the effect of Piracetam at a cellular level was determined. To achieve this purpose the effect of a 24‐hour exposure to 0–70 mM Piracetam on the growth of the L929 cell line and chick embryonic neurons in vitro was investigated. No statistically significant changes in cell viability or number was observed at 0–7 mM Piracetam in both cell types, although at 70 mM cell viability in the L929 cell line was significantly reduced when compared with the control. Initial studies indicate that Piacetam is only toxic at concentrations greater than 70 mM; however, the effects of repeated dosages over long periods still need to be investigated.

Piracetam improves mitochondrial dysfunction following oxidative stress

1.--Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. 2.--Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. 3.--Piracetam treatment at concentrations between 100 and 1000 microM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 microM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. 4.--Piracetam treatment (100-500 mg kg(-1) daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. 5.--In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients.

P.5.081 Nitric oxide and oxidative stress in the mechanisms of dopaminergic neurotoxicity: Possible neuroprotective approaches

Piracetam is a cyclic derivative of γ-aminobutyric acid (GABA). It was the first nootropic drug approved for clinical use. However, mechanism of its action is still not clear. In present paper, I investigated effects of piracetam on neurotransmitter release, plasma membrane potential monitored by fluorescent dye DiSC3(5) and chloride transport monitored by fluorescent dye SPQ in rat brain synaptosomes. It was shown that piracetam (1 mM) induces slow weak plasma membrane depolarization. This effect was decreased on 43% and 58% by both AMPA/kainate receptor blockers NBQX (10 μM) and CNQX (100 μM), respectively, on 84% by GABA ionotropic receptor blocker picrotoxin (50 μM) and on 91% upon withdrawal of HCO3− ions from incubation medium. GABA (1 mM) and kainate (100 μM) were found not to produce changes of plasma membrane potential. Also, it was found that piracetam induces chloride efflux which seems to be the reason of depolarization. Thereby, piracetam induces depolarization of plasma membrane of isolated neuronal presynaptic endings by picrotoxin-sensitive way.