Effects Of Piracetam Research Articles

Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats

In this study, we investigated the effects of the memory-enhancing drugs piracetam, vincamine, and vinpocetine or the cholinesterase inhibitor donepezil on the development of oxidative stress, inflammation, and brain damage induced in rat brain by aluminum chloride (AlCl3). Saline (control), piracetam (100 or 300 mg/kg), vincamine (10 or 20 mg/kg), vinpocetine (10 or 20 mg/kg), piracetam 100 mg/kg plus vincamine 10 mg/kg, piracetam 100 mg/kg plus vinpocetine 10 mg/kg, or donepezil 5 mg/kg were administered once daily intraperitoneally for 45 days along with AlCl3 (10 mg/kg, intraperitoneally). Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, acetylcholinesterase (AChE), butrylcholinesterase (BChE), paraoxonase (PON1) activities, and prostaglandin E2 (PGE2) concentrations were measured in brain. Histopathology and caspase-3 immunohistochemistry (an apoptotic marker) were also performed. Results indicated that (1) compared to controls, injection of AlCl3 significantly increased brain lipid peroxidation (MDA) and nitric oxide concentrations together with decreased GSH concentrations. PON1 activity in brain was significantly decreased, while AChE and BChE activities were significantly increased compared to control animals. Cortical atrophy, neuronal shrinkage, red neurons, surrounded by vacuolations with cytoplasmic neurofibrillary tangles, intense caspase-3 expression in degenerated neurons, and amyloid deposition were observed; (2) in AlCl3-treated rats, (i) lipid peroxidation was significantly decreased by the lower doses of piracetam, vincamine, and vinpocetine as well as by piracetam plus either vincamine or vinpocetine; (ii) nitric oxide was significantly decreased by the lower doses of piracetam, and vinpocetine, by both doses of vincamine, and by piracetam plus either vincamine or vinpocetine; (iii) nitric oxide also showed significant decrease after treatment with donepezil; (iv) both GSH and PON1 activity showed significant increase following the administration of the test drugs; (v) PGE2 significantly increased by the higher dose of piracetam, vincamine, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vi) AChE and BChE activities decreased after treatment with the lower dose of piracetam, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vii) AChE activity decreased following 20 mg/kg vincamine, and BChE activity decreased following 10 mg/kg vincamine; (viii) AChE but not BChE activity decreased after donepezil; (ix) on histopathology, the low dose of singly used drugs and donepezil had the best improvement in neuronal look, cortical thickness, and degree of vascular congestion. Rats treated with 10 mg/kg vinpocetine showed decreased capsase-3 immunoreactivity in brain and regenerating neurons. These results suggest that while the low therapeutic doses of the nootropic drugs piracetam, vincamine, and vinpocetine display anti-oxidant and neuroptotective effects, their high doses are likely to have prooxidant and proinflammatory properties.

Effect of piracetam and nimodipine on full-thickness skin burns in rabbits.

The potential of several drugs for full-thickness skin burns has been investigated, but the treatment of such burns remains a challenge in plastic surgery. The present study was designed to determine the effect of systemic and topical administration of piracetam and nimodipine on full-thickness skin burn wound healing. A total of 36 New Zealand male rabbits were divided into six groups. Full-thickness skin burns were produced in all the groups, except the control group. Piracetam was administered systemically (piracetam-IV) and topically (piracetam-C) for 14 days, and nimodipine was administered systemically (nimodipine-IV) and topically (nimodipine-C) over the burn wounds for 14 days. The sham group underwent burn injury but was not administered any drug. After 21 days, gross examination and histopathological analysis were performed and the results were compared statistically. Nimodipine-C and nimodipine-IV had no effect on burn wound healing. However, both piracetam-IV and piracetam-C significantly enhanced the healing of the full-thickness skin burn wounds, although the latter was more effective, useful and practical in burn wound healing. The histopathological features of the wounds in the piracetam-C group were closer to those of the control group than those of the other groups. Piracetam-C rather than piracetam-IV may promote full-thickness burn wound healing in rabbits.

The effects of piracetam on heroin-induced CPP and neuronal apoptosis in rats

BackgroundPiracetam is a positive allosteric modulator of the AMPA receptor that has been used in the treatment of cognitive disorders for decades. Recent surveys and drug analyses have demonstrated that a heroin mixture adulterated with piracetam has spread rapidly in heroin addicts in China, but its addictive properties and the damage it causes to the central neural system are currently unknown. MethodsThe effect of piracetam on the reward properties of heroin was assessed by conditioned place preference (CPP). Electron microscopy and radioimmunoassay were used to compare the effects of heroin mixed with equivalent piracetam (HP) and heroin alone on neuronal apoptosis and the levels of beta-endorphin (β-EP) in different brain subregions within the corticolimbic system, respectively. ResultsPiracetam significantly enhanced heroin-induced CPP expression while piracetam itself didn’t induce CPP. Morphological observations showed that HP-treated rats had less neuronal apoptosis than heroin-treated group. Interestingly, HP normalized the levels of β-EP in the medial prefrontal cortex (mPFC) and core of the nucleus accumbens (AcbC) subregions, in where heroin-treated rats showed decreased levels of β-EP. ConclusionsThese results indicate that piracetam potentiate the heroin-induced CPP and protect neurons from heroin-induced apoptosis. The protective role of HP might be related to the restoration of β-EP levels by piracetam. Our findings may provide a potential interpretation for the growing trend of HP abuse in addicts in China.

Modulation Effects of Piracetam and Ginkgo biloba on the Cognitive and Working Memory Functions: Psychometric Study

Extracts of Ginkgo biloba have been broadly prescribed for the treatment of cognitive dysfunction ranging in severity from mild to severe memory loss. Piracetam is a nootropic remedy correlated to inhibitory γ-aminobutyric acid (GABA) neurotransmitter. It improves cognitive function without sedation. Objective: The aim in the attending study is to evaluate the outcome of Ginkgo biloba and or piracetam on cognitive, psychomotor performances and working memory functions in normal healthy volunteers. Methods: Thirty subjects (all are males) arbitrarily chosen from medical college students. The contributors were allowed to perform mutually on the psychomotor performance device tester and the computerized n-back test (working memory task) to obtain knowledge from those tests sooner before the commencing of the examination. All psychometric response time and working memory test parameters were calculated previous to the experimental research, so the identical volunteers considered as control and through four days of receiving the Ginkgo biloba 60mg/day (trunature GSL), piracetam 800mg/day (nootropil) or both drugs. The enrolled participants were divided into three groups. Group (A) were given Ginkgo biloba, group (B) were given piracetam and group (C) were given piracetam and Ginkgo biloba. Results: Piractam significantly improves cognitive and working memory at all levels (P value is <0.05) while; it showed insignificant effects on psychometric reaction time parameters except it ameliorates the total reaction time (TRT) (P value is <0.05). The differential effects of Ginkgo biloba showed significant effects on psychometric reaction time and cognitive central Integrity (P value is <0.05) and insignificant effects on working memory accuracy except at І-Back level where it produced significant effects P<0.05. Combined effects of ginko biloba and piracetam on psychomotor performances, cognitive function and working memory produced significant effects (P value is <0.05). Conclusion: Combined effects of piracetam and Ginkgo biloba produced more significant effects on psychomotor performances and working memory functions in healthy young subjects than either Ginkgo biloba or piracetam alone in healthy young subjects. Keywords: Cognitive function, Ginkgo biloba, piracetam, psychomotor, working memory.

The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation

This study was performed to investigate the involvement of mitochondrion-specific endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown the antiapoptotic effects of piracetam but the mechanism of action of piracetam is still an enigma. To assess the involvement of endonuclease G in piracetam-induced protective effects, astrocyte glial cells were treated with lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation, and DNA fragmentation, which were attenuated by piracetam cotreatment. Cotreatment of astrocytes with piracetam showed its significantly time-dependent absorption as observed with high-performance liquid chromatography. Astrocytes treated with piracetam alone showed enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS-treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of the terminal executor of the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment attenuated the LPS-induced endonuclease G translocation. In conclusion this study indicates that LPS treatment of astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and translocation of endonuclease G to the nucleus, which was inhibited by piracetam cotreatment, confirming that the mitochondrion-specific endonuclease G is one of the factors involved in piracetam-induced protective mechanisms.

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2weeks in doses of 50, 100 and 200mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

Modulation Effects of Piracetam and Ginkgo Biloba on the Cognitive and Working Memory Functions: Psychometric Study

Extracts of ginkgo biloba have been broadly prescribed toward advance symptoms of cognitive dysfunction ranging in severity from mild memory loss to dementia also; in delaying the development of dementia; ginkgo biloba has been encouraged commercially as a smart medicine to augment the brain function of healthy people. Piracetam is a no tropic remedy correlated to inhibitory γ-aminobutyric acid (GABA) neurotransmitter. Piracetam may be the initial agent acting on cognitive function without sedation. Thirty subjects (30 males) arbitrarily choose as of medical college students. The contributors were allowable to perform mutually on the psychomotor performance device tester and the computerized n-back test (working memory task) to obtain knowledge from those tests sooner than the commencing of the examination. All psychometric response time and working memory test parameters calculated previous to the experimental research, so the identical volunteers considered as control and through four days of receiving the ginkgo biloba 60mg/day (trunature GSL),piracetam 800 mg/day (neutrophil) or both drugs so the enrolled participants divided into three groups .Group A take ginkgo biloba, group B take piracetam and group C take piracetam and ginkgo biloba. Piracetam significantly improve cognitive and working memory at all levels P<0.05 while it showed insignificant effects on psychometric reaction time parameters except it ameliorate the total reaction time (TRT) P <0.05. The differential effects of ginkgo biloba showed significant effects on psychometric reaction time and cognitive central Integrity P<0.05 and insignificant effects on working memory accuracy except at level І-Back where it produced significant effects P<0.05. Combined effects of ginko biloba and piracetam on psychomotor performances, cognitive function and working memory produced significant effects P <0.05. Conclusion: Combined effects of piracetam and ginkgo biloba produced more significant effects than either ginkgo biloba or piracetam alone on cognitive function and working memory.

Effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery: A meta-analysis

Cognitive impairments are observed in numerous patients following coronary bypass surgery, and piracetam are nootropic compounds that modulate cerebral functions by directly enhancing cognitive processes. The present meta-analysis was conducted to evaluate the protective effect of piracetam on the cognitive performance of patients undergoing coronary bypass surgery. The relevant studies were identified by searching Medline, EMBASE, PubMed and the Cochrane Library up to June 2013 and the pertinent bibliographies from the retrieved studies were reviewed. Data were selected from the studies according to predefined criteria. The meta-analysis included two randomized control trials involving 184 patients and including the Syndrom-Kurz test (SKT). Findings of the meta-analysis showed that following treatment the change from baseline observed in five SKT subtest scores, conducted with piracetam patients, indicated a significant advantage over those patients that were in the placebo group. The subtests included immediate pictured object recall, weighted mean difference (WMD)=0.91, 95% confidence interval (CI) 0.51–1.31, P<0.00001; delayed pictured object recall, WMD=0.74, 95% CI 0.19–1.28, P=0.008; delayed picture recognition, WMD=0.82, 95% CI 0.31–1.31, P=0.001; immediate word recall, WMD=0.87, 95% CI 0.47–1.28, P<0.0001; and letter interference, WMD=3.46, 95% CI −5.69 to −1.23, P=0.002. These results indicated that piracetam may have been effective in improving the short-term cognitive performance of patients undergoing coronary bypass surgery. High quality, well-controlled and longer randomized trials are required to corroborate this result.

Comparison of the effectiveness of intravenous piracetam and intravenous dimenhydrinate in the treatment of acute peripheral vertigo in the emergency department

We aimed to compare the effectiveness of intravenous piracetam with that of intravenous dimenhydrinate in the treatment of acute peripheral vertigo in the emergency department. This double-blind study comprised a total of 200 patients, aged between 18 and 70 years, who had presented to the emergency department of Ankara Training and Research Hospital and were diagnosed with peripheral vertigo. Evaluation of the severity of the patients' vertigo was performed using a visual analogue scale, before and after drug administration. Both drugs were found to be effective (p < 0.001) and had comparable effects (p < 0.474). Dimenhydrinate was also found to have about two times the side effects of piracetam. Drowsiness was found to be the most common side effect of these two drugs. Dimenhydrinate and piracetam have similar levels of effectiveness with regard to acute vertigo. We conclude that piracetam, which has fewer side effects than dimenhydrinate, better vestibular compensation, and is effective for both acute and chronic vertigo, could be more frequently used in the emergency treatment of acute vertigo.

Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam

The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

Piracetam induces plasma membrane depolarization in rat brain synaptosomes

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 (1mM) induces slow weak plasma membrane depolarization. This effect was decreased on 43% and 58% by both AMPA/kainate receptor blockers NBQX (10μM) and CNQX (100μM), respectively, on 84% by GABA ionotropic receptor blocker picrotoxin (50μM) and on 91% upon withdrawal of HCO3− ions from incubation medium. GABA (1mM) and kainate (100μM) 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.

A novel CaV2.2 channel inhibition by piracetam in peripheral and central neurons

No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.2 channels in peripheral neurons, using patch-clamp recordings from cultured superior cervical ganglion neurons. In addition, we tested if Ca(V)2.2 channel inhibition could be related with the effects of piracetam on central neurons. We found that piracetam inhibited native Ca(V)2.2 channels in superior cervical ganglion neurons in a dose-dependent manner, with an IC(50) of 3.4 μmol/L and a Hill coefficient of 1.1. GDPβS dialysis did not prevent piracetam-induced inhibition of Ca(V)2.2 channels and G-protein-coupled receptor activation by noradrenaline did not occlude the piracetam effect. Piracetam altered the biophysical characteristics of Ca(V)2.2 channel such as facilitation ratio. In hippocampal slices, piracetam and ω-conotoxin GVIA diminished the frequency of excitatory postsynaptic potentials and action potentials. Our results provide evidence of piracetam's actions on Ca(V)2.2 channels in peripheral neurons, which might explain some of its nootropic effects in central neurons.

Piracetam for acute ischaemic stroke

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

Piracetam, an AMPAkine drug, facilitates memory consolidation in the day-old chick

Piracetam is an AMPAkine drug that may have a range of different mechanisms at the cellular level, and which has been shown to facilitate memory, amongst its other effects. This series of experiments demonstrated that a 10mg/kg dose of piracetam facilitated memory consolidation in the day-old chick when injected from immediately until 120min after weak training (i.e. using a 20% v/v concentration of methyl anthranilate) with the passive avoidance learning task. Administration of piracetam immediately after training led to memory facilitation which lasted for up to 24h following training. This dose of the AMPAkine was not shown to facilitate memory reconsolidation. These findings support the contention that application of the AMPAkine piracetam facilitates memory using a weak training task, and extend the range of actions previously noted with NMDA-related agents to those which also facilitate the AMPA receptor.

Piracetam‐induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases

We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations.

Piracetam for fetal distress in labour

Piracetam is thought to promote the metabolism of brain cells when they are hypoxic. It has been used to prevent adverse effects of fetal distress. The objective of this review was to assess the effects of piracetam for suspected fetal distress in labour on method of delivery and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012). Randomised trials of piracetam compared with placebo or no treatment for suspected fetal distress in labour. Both review authors assessed eligibility and trial quality. One study of 96 women was included. Piracetam compared with placebo was associated with a trend to reduced need for caesarean section (risk ratio 0.57, 95% confidence interval 0.32 to 1.03). There were no statistically significant differences between the piracetam and placebo group for neonatal morbidity (measured by neonatal respiratory distress) or Apgar score. There is not enough evidence to evaluate the use of piracetam for fetal distress in labour.

Could piracetam potentiate behavioural effects of psychostimulants?

Press and internet reports mention abuse of nootropic drug piracetam (PIR) in combination with psychostimulants methamphetamine (MET) or 4-methylenedioxymethamphetamine (MDMA). These combinations are believed to produce more profound desirable effects, while decreasing hangover. However, there is a lack of valid experimental studies on such drug–drug interactions in the scientific literature available. Our hypothesis proposes that a functional interaction exists between PIR and amphetamine psychostimulants (MET and MDMA) which can potentiate psychostimulant behavioural effects.Our hypothesis is supported by the results of our pilot experiment testing acute effects of drugs given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA 2.5mg/kg, n=11; PIR 300mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant changes in mouse locomotor/exploratory behaviour, whereas the same dose combined with either MET or MDMA significantly enhanced their stimulatory effects.Different possible neurobiological mechanism underlying drug–drug interaction of PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic or cholinergic brain systems. However, the interaction with membrane phospholipids seems as the most plausible mechanism explaining PIR action on activities of neurotransmitter systems.Despite that our behavioural experiment cannot serve for explanation of the pharmacological mechanisms of these functional interactions, it shows that PIR effects can increase behavioural stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or MDMA by human abusers is not perhaps a coincidental phenomenon and may be based on existing PIR potential to intensify acute psychostimulant effects of these drugs of abuse.

Buyuan Congnao decoction decreases hippocampal beta-amyloid expression in a rat model of Alzheimer's disease.

A mixture of ibotenic acid and β-amyloid 1–42 was injected into the hippocampus of a rat model of Alzheimer's disease, followed by intragastric administration of a traditional Chinese medicine Buyuan Congnao decoction (main components included radix astragali, radix polygoni multiflori preparata, rhizoma acori talarinowii, radix polygalae, fructus alpiniae oxyphyllae, and radix glycyrrhizae preparata) and a piracetam suspension. Following treatment with traditional Chinese medicine or western medicine, β-amyloid expression decreased and neuronal morphology was normal in the rat hippocampal CA1 region, in addition to significantly shortened average latency in the Morris water navigation task. These findings suggested that compound prescription of Buyuan Congnao decoction, similar to the curative effects of piracetam, decreased hippocampal β-amyloid expression in a rat model of Alzheimer's disease, as well as improved learning and memory.

Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats

Organophosphate pesticides, such as phosphamidon (PHOS), have been shown to adversely affect memory and induce oxidative stress after both acute and chronic exposure. The present study was therefore designed to investigate the effects of piracetam (PIR) and vitamin E on PHOS-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and a prolongation of TL in the PHOS (1.74 mg/kg/day per oral; p.o.)-treated group at weeks 6 and 8, as compared to the control group. Administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) for 2 weeks antagonized the effect of PHOS on SDL as well as TL. PHOS per se produced a significant increase in brain MDA levels and a decrease in brain NP-SH levels, whereas administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) attenuated these effects. Thus, the results of the study showed that both PIR and vitamin E attenuated the cognitive dysfunction and oxidative stress induced by PHOS in the rat brain.