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Stroke is a sudden cerebral root neurologic collapse, a major cause for global morbidity and death, necessitates the use of neuroprotectants to prevent further damage to ischemic decline. Citicoline and piracetam are widely used as neuro-protectives, however their benefits in Acute Ischemic Stroke have not yet been established. This prospective, quasi-experimental study compared the effectiveness of citicoline (Group A) and citicoline with piracetam combination (Group B) in moderate-to-severe patients. 75 patients were divided into two groups (25 in Group A and 50 in Group B) and followed for a period of 90 days. Their cognitive and functioning events were examined using National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI). There is no discernible difference (p > 0.05) amongst the two groups by NIHSS whereas, there was a significant difference (p<0.05) in mRS and BI. After 90 days, Group A patients significantly progressed in terms of overall functional and cognitive improvement. The administration of citicoline within the first 24 hours of a stroke helps to prevent further sequelae and minimizes the severity of AIS. This study concludes that citicoline alone responds better than piracetam combination, but its neuroprotective properties have not been proven. [ABSTRACT FROM AUTHOR]

Annually, 172 million fall events cause temporary or permanent impairment in older adults, and this number is increasing. Contributing factors that increase the risk for falls include age, polypharmacy, and malnutrition. This study evaluated medications mainly included in the EU(7)-PIM (potentially inappropriate medication) list. From March 21, 2022, to July 6, 2022, 945 patients who experienced a fall and visited the Department of Emergency Medicine at the Albert Szent-Györgyi Health Centre of the University of Szeged in Hungary. Data from 886 patients were collected (study group). The control group included 1364 patient data collected from three general practice in Hungary. The use of ≥ 2 EU(7)-PIM drugs was found to be associated with increased risk for falls (adjusted odds ratio [AOR], 1.38; 95% confidence interval [CI] 1.01–1.88). Piracetam (AOR, 1.81; 95% CI, 1.28–2.57) and trimetazidine (AOR, 1.62; 95% CI, 1.17–2.24) were associated with increased risk for falls. Doxazosin was associated with a low risk for falls (AOR, 0.59; 95% CI, 0.41–0.86). Tiapride (AOR, 3.54; 95% CI, 1.75–7.17), gliclazide (AOR, 1.57; 95% CI, 1.02–2.43), and vinpocetine (AOR, 1.95; 95% CI, 1.29–2.95) are not included in the EU(7)-PIM list; however, they are associated with increased risk for falls. Long-acting benzodiazepines (AOR, 1.79; 95% CI, 1.20–2.68), antidepressants (AOR, 1.89; 95% 95% CI, 1.37–2.61), serotonin–norepinephrine reuptake inhibitor (AOR, 2.82; 95% CI, 1.41–5.67; p < 0.01), and selective serotonin reuptake inhibitor (AOR, 1.88; 95% CI, 1.24–2.85) were also associated with increased risk for falls. However, Z-drugs were associated with a low risk for falls (AOR, 0.57; 95% CI, 0.36–0.92). With the help of this tool, trimetazidine and piracetam are filtered as EU(7)-PIM drugs associated with increased risk for falls. [ABSTRACT FROM AUTHOR]

Epilepsy, a category of neurological disorder, is characterized by recurrent seizures. Epileptic seizures are characterized by sudden alterations in brain electrical activity. Piracetam is a derivative of cyclic aminobutyric acid that exerts neuroprotective effects. The objective of this study was to evaluate the neuroprotective, anticonvulsant, and antianxiety effects of piracetam in the pentylenetetrazole (PTZ) seizure rat model. To evaluate the anticonvulsant properties of piracetam in the PTZ seizure model, the experimental groups were administered piracetam at doses of 30 or 100 mg/kg. The positive control group was administered diazepam (2 mg/kg), while the negative control group was treated with only PTZ. The anti-anxiety effects were evaluated using the elevated plus maze and open field tests. Additionally, the antioxidant effects of piracetam on brain tissues were examined. The open field test results demonstrated a significant increase in the number of crossings over the line in the Piracetam (30 and 100 mg/kg) and diazepam groups, in comparison to the negative control group. In the plus maze test, the groups administered Piracetam demonstrated a greater tendency to spend time in the open arms than the control group. Furthermore, diazepam markedly elevated the time spent in the open arms in comparison to the negative control group. The histological results demonstrated structural alterations in hippocampal neurons. Additionally, the antioxidant test demonstrated that Piracetam possesses antioxidant properties when compared to the negative control group. Piracetam demonstrated anticonvulsant and neuroprotective effects in PTZ-induced epileptic rats, exhibiting the ability to inhibit or reduce the incidence of seizures. Additionally, it demonstrated anti-anxiety and sedative properties. The neuroprotective effects of Piracetam may be attributed to its ability to regulate neurotransmitter systems, including cholinergic, serotonergic, noradrenergic, and glutamatergic pathways. It can be posited that Piracetam may possess neuroprotective, anti-epileptic, anti-anxiety, and antioxidant properties in PTZ epileptic rats. Nevertheless, additional research is required to substantiate these findings. [ABSTRACT FROM AUTHOR]

With the aim to identify novel and improved drug candidates for the non‐opioid management of neuropathic pain, a few chiral fluorobenzenesulfonylamide derivatives of 1,4‐diazabicyclo[4.3.0]nonan‐9‐one, a rigid bicyclic analogue of piracetam, were prepared and characterized in animal models of chemotherapy‐induced neuropathic pain. The R‐enantiomers of these novel compounds are generally more potent than their corresponding S‐enantiomers. An oral dose of R‐2‐fluorophenyl derivative 8a is better tolerated when compared to the R‐3‐ fluorophenyl derivative 9a, (mouse Rota‐Rod test). Consequently, the enantiomeric 2‐fluorophenyl derivatives (8a and 8b) are thoroughly investigated in an enlarged panel of inflammatory and neuropathic pain models, including several models of chemotherapy‐induced neuropathic pain. The R‐enantiomer (8a) is consistently more potent in its anti‐hypersensitivity profile than the S‐enantiomer (8b). Surprisingly, the non‐racemic enantiomeric mixture consisting of a 2‐to‐1, or better still, a 3‐to‐1 mixture of the R‐enantiomer (8a) over the S‐enantiomer (8b) is more potent than the R‐enantiomer (8a) alone or than their racemic mixture. These results are reminiscent of our previous report on MP‐101, a non‐racemic mixture of dimiracetam enantiomers. Although further investigations will be required to rationalize these findings at the pharmacokinetic or molecular level, racetam derivatives appear to be promising candidates for the management of persistent pain. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD. [ABSTRACT FROM AUTHOR]

Breath-holding spells are a benign condition primarily seen in 3% to 5% of healthy children aged between six months and five years. Although no specific treatment is recommended due to its benign nature, iron and piracetam are used in severe or recurrent cases. We planned to compare the heart rate variability (HRV) before and after treatment with 24-hour Holter monitoring in patients receiving iron and piracetam treatment and investigate the treatment's effectiveness. Twenty-five patients who applied to the outpatient clinic between 2013 and 2015 due to breath-holding spells were included in the study. The patients who received piracetam and iron therapy and underwent 24-hour rhythm Holter monitoring were evaluated retrospectively. Fourteen (56%) of these patients were evaluated as having cyanotic-type and 11 (44%) patients were assessed as having pale-type breath-holding spells. A significant difference was found only between hourly peak heart rate and total power in the group receiving iron treatment. Significant differences were also found among the minimum heart rate, mean heart rate, the standard deviation of RR intervals, the mean square root of the sum of the squares of their difference between adjacent RR intervals, spectpow, and low frequency before and after the treatment in the patients who started piracetam treatment (P < 0.05). Our study is critical as it is the first to investigate the effects of treatment options on various HRV in patients with breath-holding spells. There were statistically significant changes in HRV parameters in patients receiving piracetam, and the number of attacks decreased significantly. Piracetam treatment contributes positively to the breath-holding spell with regard to efficacy and HRV, therefore it can be used to treat breath-holding spells. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients. Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months. Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients. Trial registration: ChiCTR2000040466, date of registration: November 28, 2020.

Piracetam has been available on the market since 1971. Its primary indication is the age-related memory decline. The objective of this review is to highlight the controversies surrounding in the use of piracetam. Piracetam modulates membrane fluidity, which is decreased in the elderly, and this explains its effects on the vascular and nervous system. The scientific literature on piracetam is extensive; nevertheless, Cochrane systematic reviews raised serios concerns about the efficacy of this pharmacon in the treatment of dementia, cognitive decline, aphasia in post-stroke, and the prophylaxis of vasoocclusive sickle cell disease crises. However, in the treatment of acute vertigo and cortical myoclonus, its efficacy appears to be supported by several studies. The indications for drugs containing piracetam in Hungary are diverse. Furthermore, in the SPC, memory deterioration is mentioned as an indicator; nevertheless, the package leaflet emphasizes the improvement of brain functions (e.g. learning). Despite these facts, the use of piracetam in Hungary is still significant, approximately 10,000 inhabitants used this active substance every day in 2022, in the defined daily dose (DDD – 2400 mg). Based on European medicine databases, the availability, indications and daily dose of piracetam in cognitive decline vary by country to country in Europe. In the United States, no piracetam-containing drugs have been approved, and the FDA did not support the use of piracetam in food supplements. Dementia and cognitive decline are more prevalent in elderly; nonetheless, international and Hungarian guidelines do not support the use of piracetam in dementia or cognitive decline indications, nor do lists and screening tools (PIM lists). In Hungary, piracetam is commonly used to treat dementia and cognitive decline; however, its efficacy is questioned due to a lack of data. As a result, the use of this pharmacon in this indication lacks evidence-based support.

Delirium is a commonly seen neuropsychiatric disorder that may extend over time, lasting for more than 60 days, thus increasing the risk of cognitive and behavioral outcomes in patients. Electroconvulsive therapy (ECT) is one of the treatment modalities for behavior control but may be associated with rare complications such as tardive seizure, convulsive status epilepticus, and prolonged postictal confusion. We report a case of acute psychosis who was given consecutive 2 ECTs, after which she developed probable tardive seizure in the recovery period, followed by status epilepticus and extended delirium lasting for more than 2½ months, but was misdiagnosed as psychosis and treated with several antipsychotic medications. As there was no improvement in her condition, she was then transferred to a tertiary center for further management.

OBJECTIVE: To explore the effects of Bifidobacterium quadruple viable tablet combined with piracetam on gastrointestinal function and neurological function in patients with severe cerebral hemorrhage. METHODS: Fifty patients with severe cerebral hemorrhage admitted into the hospital from 2021 to 2022 were extracted to be divided into the control group ( n = 24) and study group ( n = 26) via the random number table method. The control group was treated with piracetam, while the study group received Bifidobacterium quadruple viable tablet combined with piracetam. The average cerebrovascular flow rate, average cerebrovascular flow, vascular peripheral resistance and dynamic resistance level were detected. The Glasgow coma score (GCS) and activities of daily living (ADL) scores were used to assess the degree of coma and ability to perform activities of daily living. Lactobacillus, Bifidobacterium, D-lactic acid ( D-LC), diamine oxidase ( DAO), neuropeptide Y ( NPY) and ferritin level were detected. The national institutes of health neurologic deficit scale for stroke (NIHSS) was used to assess the neurologic deficits. Therapeutic effect of two groups was compared. RESULTS: After treatment, the mean cerebrovascular flow rate, mean cerebrovascular flow level, GCS, ADL scores of the study group were higher than those of the control group; the peripheral vascular resistance, dynamic resistance, D-LC, DAO, NPY, ferritin, NIHSS scores of the study group were lower than those of the control group, with statistically significant differences (P<0. 05). After treatment, the total effective rate of the study group was 92. 31% ( 24 / 26), higher than 66. 67% ( 16 / 24) of the control group, the difference was statistically significant (P<0. 05). CONCLUSIONS: Bifidobacterium quadruple viable tablet combined with piracetam can significantly restore the gastrointestinal function and neurological function of patients with severe cerebral hemorrhage, improve the cerebrovascular function, restore the balance of intestinal flora, enhance the conscious state, improve the ability of daily life, and the clinical therapeutic effect is remarkable. [ABSTRACT FROM AUTHOR]

AbstractAimMaterials and methodsResultsLimitationsConclusionsThis work explores the effect of Cisplatin—a chemotherapeutic agent known to cause deterioration in cognitive function in cancer patients, and spatial memory in mice. It also investigates the potential neuroprotective effects of Piracetam, which is a nootropic drug recognized for improving cognitive ability.The study incorporates four groups of mice receiving varied medication regimens, with memory tested using the Novel Location Recognition (NLR) method.The findings from our study revealed that memory decline and a suppression of cellular proliferation were observed in adult male mice subjected to Cisplatin treatment; furthermore, a decline in antioxidant efficacy within the hippocampal dentate gyrus was evident. Moreover, analysis of treatment effects on the animals’ weight revealed that the Cisplatin and Piracetam group exhibited the most significant weight loss during drug administration. Despite the significant weight loss, the simultaneous use of Cisplatin and Piracetam demonstrated a notable improvement in memory and an augmentation of hippocampal proliferation and antioxidant effect.It is important to note that our study was hampered by budget limits, a lack of additional animals, and mice’s low tolerance for protracted treatment.Should the outcomes of Piracetam observed in this investigation be applicable to patients, it might offer a relatively straightforward approach to mitigate the cognitive impacts endured by cancer survivors following exposure to chemotherapy. Future research will be needed to study Piracetam’s effect on mice with brain cancer after Cisplatin treatment in order to extrapolate the results onto cancer patients. [ABSTRACT FROM AUTHOR]

Delirium is a commonly seen neuropsychiatric disorder that may extend over time, lasting for more than 60 days, thus increasing the risk of cognitive and behavioral outcomes in patients. Electroconvulsive therapy (ECT) is one of the treatment modalities for behavior control but may be associated with rare complications such as tardive seizure, convulsive status epilepticus, and prolonged postictal confusion. We report a case of acute psychosis who was given consecutive 2 ECTs, after which she developed probable tardive seizure in the recovery period, followed by status epilepticus and extended delirium lasting for more than 2½ months, but was misdiagnosed as psychosis and treated with several antipsychotic medications. As there was no improvement in her condition, she was then transferred to a tertiary center for further management. [ABSTRACT FROM AUTHOR]

Piracetam is the most widely used drug in breath-holding spells (BHS); however, its efficacy might not be satisfying to parents. This study aimed to compare the efficacy of docosahexaenoic acid (DHA) plus piracetam with piracetam alone in reducing the frequency and severity of BHS in infants and preschool children. This randomized clinical trial included two groups diagnosed with BHS. Group I included 50 patients who received DHA plus piracetam. Group II (control group) included 50 children who were managed with piracetam plus a placebo. Children were re-evaluated at one, three, and six months after treatment. Occurrences of BHS and drug side effects were recorded. The primary outcome was to evaluate the effect of the combined treatment of piracetam and DHA on the frequency and severity of spells. BHS were reported in only 16% of children six months after treatment with piracetam and DHA compared with 50% of those treated with piracetam only (P value = 0.001). DHA plus piracetam is more effective than piracetam alone in decreasing the frequency and severity of BHS in children. [ABSTRACT FROM AUTHOR]

Abstract—Based on the special role of the β-arrestin signal protein in the processes of neuronal plasticity and receptor activation, the effects of the nootropic drugs Piracetam (2-oxo-1-pyrrodinyl-acetamide, UCB 6215, 200 mg/kg, IP), and Noopept (ethyl ether N-phenyl-acetyl-L-prolyl-glycine, GVS-111, 0.5 mg/kg, IP) were studied in mice with congenital deficiency of β-arrestin-2 (BARR2-KO mice) and in C57Bl/6 mice (wild type for the BARR2-KO, WT strain). Serotonin (5-HT)2A) and NMDA-receptors of the brain, which play an important role in cognitive processes but differ in structure and activation mechanism, were chosen as the objects of the study. Using radioligand analysis, it was found that the BARR2-KO mice differ from the C57Bl/6 in significantly higher density (Bmax) of both NMDA-receptors in the hippocampus (by 85%) and 5-HT2A-receptors in the cerebral cortex (by 54%). Interestingly, both drugs after chronic administration increased the number of NMDA-receptors in the hippocampus in both BARR2-KO (Piracetam by 76% and Noopept by 78%) and C57Bl/6 strains (Piracetam by 112% and Noopept by 49%). At the same time, the effects of both drugs on the density of serotonin 5-HT2A-receptors in BARR2-KO and C57Bl/6 mice were not the same. In particular, Piracetam caused an increase in the density of 5-HT2A-receptors in the cerebral cortex of BARR2-KO mice by 31%, whereas, in the C57Bl/6, neither Piracetam nor Noopept had any effect. Thus, the absence of the β-arrestin signaling protein in BARR2-KO mice is accompanied by an increase in the density of NMDA- and 5-HT2A-receptors in the brain. At the same time, the different effects of Piracetam and Noopept on NMDA-receptors both in the mice with congenital β-arrestin deficiency and in the strain with normal expression may indicate that this type of receptors is a common primary target for the action of nootropics of various structures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Epilepsy, a neurodegenerative disorder, continues to throw challenges in the therapeutic management. The current study sought to ascertain if the therapeutic interactions between piracetam and diethylstilbestrol may prevent grand-mal seizures in rats. MATERIALS AND METHODS: Piracetam (PIR; 10 and 20 mg/kg) and diethylstilbestrol (DES; 10 and 20 mg/kg) alone as a low-dose combination were administered to rats for 14 days. The electroshock (MES; 180 mA, 220 V for 0.20 s) was delivered via auricular electrodes on the last day of treatment and rats were monitored for convulsive behavior. To elucidate the mechanism, hippocampal mechanistic target of rapamycin (mTOR) and interleukin (IL)-1ß, IL-6 and tumor necrotic factor-alpha (TNF-a) levels were quantified. Hippocampal histopathology was conducted to study neuroprotective effect of drug/s. In vitro studies and in silico studies were conducted in parallel. RESULTS: To our surprise, the low dose of the combination regimen of PIR (10 mg/kg) and DES (10 mg/kg) unfolded synergistic anti-seizure potential, with brimming neuroprotective properties. The mechanism could be related to a significant reduction in the levels of hippocampal mTOR and proinflammatory cytokines. The docking scores revealed higher affinities for phosphatidylinositol 3-kinase (PI3K) in co-bound complex, and when docking DES first, while better affinities for protein kinase B (Akt) were revealed when docking PIR first (both drugs bind cooperatively as well). This indicated that the entire PI3K/Akt/mTOR signaling pathway is intercepted by the said combination. In addition, the % of cell viability of HEK-293 cells [pre-exposed to pentylenetetrazol (PTZ)] was increased by 327.29% compared to PTZ-treated cells (toxic control; 85.16%). CONCLUSIONS: We are the first to report the promising efficacy of the combination (PIR 10 mg/kg + DES 10 mg/kg) to restrain seizures and epileptogenic changes induced by electroshock by a novel mechanism involving inhibiting the PI3K/Akt/mTOR signaling. [ABSTRACT FROM AUTHOR]

Thiacloprid (TH) is a neurotoxic agricultural insecticide and potential food contaminant. The purpose of this study was to investigate the relationship between TH exposure and memory dysfunction in rats, as well as the potential protective effect of piracetam and piracetam-loaded magnetic chitosan nanoparticles (PMC NPs). Rats were divided into five equal groups (six rats/group). The control group received saline. Group II was treated with PMC NPs at a dose level of 200 mg/kg body weight (Bwt); Group III was treated with 1/10 LD50 of TH (65 mg/kg Bwt); Group IV was treated with TH (65 mg/kg Bwt) and piracetam (200 mg/kg Bwt); Group V was co-treated with TH (65 mg/kg Bwt) and PMC NPs (200 mg/kg Bwt). All animal groups were dosed daily for 6 weeks by oral gavage. Footprint analysis, hanging wire test, open field test, and Y-maze test were employed to assess behavioral deficits. Animals were euthanized, and brain tissues were analyzed for oxidative stress biomarkers, proinflammatory cytokines, and gene expression levels of glial fibrillary acidic protein (GFAP), amyloid-beta precursor protein (APP), B-cell lymphoma 2 (Bcl-2), and caspase-3. Brain and sciatic nerve tissues were used for the evaluation of histopathological changes and immunohistochemical expression of tau protein and nuclear factor kappa B (NF-κB), respectively. The results revealed that TH-treated rats suffered from oxidative damage and inflammatory effect on the central and peripheral nerves. The administration of PMC NPs considerably protected against TH-induced neuronal damage, increased antioxidant enzyme activity, decreased inflammatory markers, and improved behavioral performance than the group treated with piracetam. The neuroprotective effect of PMC NPs was mediated through the inhibition of GFAP, APP, caspase-3, Tau, and NF-κB gene expression with induction of Bcl-2 expression. In conclusion, TH could induce oxidative stress, inflammatory and neurobehavior impairment in rats. However, PMC NPs administration markedly mitigated TH-induced brain toxicity, possibly via oxidative and inflammatory modulation rather than using piracetam alone. [ABSTRACT FROM AUTHOR]

The effects of piracetam plus mannitol on cerebral edema, neurological function, and vascular endothelin-1 (ET-1) levels after cerebral hemorrhage were compared with those of mannitol alone. Patients with cerebral edema after cerebral hemorrhage were enrolled according to inclusion and exclusion criteria and divided into control (CON) and observation (OBS) groups using a randomized, controlled, single-blind, single-center protocol. Patients in the CON group were treated with mannitol, whereas those in the OBS group were treated with piracetam plus mannitol. The clinical efficacy and indicators of neurological function, including the brain edema volume, cerebral hemorrhage volume, Glasgow Coma Scale (GCS), activity of daily living (ADL), stroke scale (NIHSS), MOS item short from health survey (SF-36), and levels of vascular endothelin-1 at three months after treatment were evaluated in a statistical framework. The volumes of intracranial brain edema and hematoma after intracerebral hemorrhage were significantly lower in the OBS group than those in the CON group (P < 0.05). The GCS index, NIHSS score, ADL score, and SF-36 score improved significantly in the OBS group (P < 0.05) and ET-1 levels were significantly lower in the OBS group than those in the CON group (P < 0.05). Patients treated with piracetam plus mannitol showed substantial improvements in neurological function and clinical outcomes, with a significant reduction in ET-1 levels and significant enhancement in endothelial function. [ABSTRACT FROM AUTHOR]

Etoposide (ETP) is one of the leading antitumour agents in cancer chemotherapy. Many studies have reported on ETP-induced peripheral neuropathy; however, few reports have focused on its brain toxicity. The current research investigates the protective potential of taurine, piracetam and vinpocetine on serum biomarkers associated with inflammation and brain injury induced by ETP in a rodent model. A total of 30 female albino rats were equally divided into five groups; the 1st and 2nd groups were the control and ETP-treated groups, respectively, while the 3rd, 4th and 5th groups were ETP-treated rats cotreated with taurine, piracetam and vinpocetine, respectively. Administration of ETP reduced body weight significantly, enhanced production of serum proinflammatory cytokines including tumour necrosis factor-alpha, interleukin-1 beta (IL-1ß) and IL-6 and decreased glutathione serum levels. Moreover, ETP treatment resulted in upregulation of glial fibrillary acidic protein expression and histopathological alterations in the rats' brain compared to the control group. Co-treatment with taurine, piracetam and vinpocetine counteracted ETP-induced brain injury and altered serum biomarkers levels. We concluded that cotreatment with vinpocetine could serve as a complementary therapeutic agent in reducing brain injury and toxicity induced by ETP. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and Y-maze tests. Acetylcholinesterase (AChE), neuroinflammatory mediators (cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α)), apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl2 associated X protein (Bax), cysteine aspartate specific protease-3 (caspase-3)), oxidative parameters (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) were also determined in the brain. PIRA administration offered significant protection against DOX-induced cognitive deficits in all maze tests and restored cholinergic functions via a significant reduction in AChE levels. Additionally, PIRA suppressed DOX-induced neuroinflammatory mediators (COX-2, PGE2, NF-κB, and TNF-α), pro-apoptotic proteins (Bax and caspase-3), and oxidative stress (MDA). Besides, it facilitated antioxidant (CAT and GSH) levels. Hence, our study highlighted that the neuroprotective activity of PIRA against DOX-induced cognitive deficits can be linked to reductions of AChE levels, neuro-inflammatory mediators, pro-apoptotic proteins, and oxidative stress. [ABSTRACT FROM AUTHOR]

[Display omitted] • A selective molecular imprinted polymer was fabricated to detect the brain doping drug Piracetam. • Optimization of the sensor fabrication conditions was performed using quality-by-design. • Very low detection limits were reached using the proposed MIP. • Determination of Piracetam in its pharmaceutical dosage form and spiked human plasma. • The method's greenness was evaluated using GAPI and AGREE metric tools. It is encouraging to note that in recent years there has been a growth of high-quality articles detailing molecular imprinted sensors for the detection of biomolecules, illicit narcotics, and explosives, paving the way for the technology's usage in forensic and medical diagnostics. Thus in this work, a molecularly imprinted polymeric sensor was fabricated, for the first time, for the sensitive and selective determination of a brain doping agent; Piracetam, using a pencil-graphite electrode. This sensor was created by the simple anodic electro-polymerization of o-phenylenediamine (o-PD) with Piracetam as the template. Then the sensor was activated by removing the template using a suitable solvent mixture. Because of Piracetam's lack of electro-activity, [Fe (CN) 6 ]3−/4− has been used as an electrochemical probe that produces analytically relevant voltammetric signals by competing for the binding sites. Based on UV-spectrophotometric measurements, Job's approach confirmed the expected stoichiometric ratio between Piracetam and the chosen monomer. X-ray photoelectron spectroscopy and cyclic voltammetry techniques were used for the characterization of the fabricated sensors. Different factors affecting the electro-polymerization conditions as; the effect of scan rate, number of cycles, pH of electro-polymerization, and the incubation time for rebinding were studied and optimized using fractional factorial design, in which the predicted model fits well to the experimental data as proved by ANOVA results. The developed voltammetric platform was applied for the in-line quantification of Piracetam in its pure solutions, pharmaceutical dosage form, and spiked human plasma with high accuracy and selectivity without the interference of the co-formulated drug; Citicoline sodium and excipients. The proposed molecular imprinted sensor was very sensitive with a linearity range (1.00 × 10−13 − 1.00 × 10−12 M), with LOD down to 4.38 × 10−15 M. This method was statistically compared with the reported method, and no statistically significant difference was found. The proposed method was assessed for greenness quantitatively and qualitatively using the Green Analytical Procedure Index (GAPI) and Analytical GREEnness metric (AGREE) as new greenness assessment tools. [ABSTRACT FROM AUTHOR]

The effect of subchronic administration of the nootropics Phenotropil (100 mg/kg/day) on the behavior of CD-1 outbreed mice in the "closed enriched cross maze" test (CECM) was studied. Predominantly, the mouse population was divided into subpopulations according to their values of individual attention index for novel objects in the maze compartments – highly attentive (ED-high) and low attentive (ED-low). It was found that Phenotropil increased the attention index in ED-low, but disimproved it in the ED-high subpopulation, and also changed parameteres of anxiety and locomotor activity; this distinguished it from the more selective effect of Piracetam (200 mg/kg/day). The higher selectivity of Piracetam was also shown in relation to dopamine metabolism processes in the prefrontal cortex: the drug normalized the metabolic turnover of intracellular (DOPAC/DA) as well as extracellular (HVA/DA) dopamine, while Phenotropil influenced on the former only. Thus, positive effect of Piracetam on the attention level in ED-low mice corresponds to the normalization of both indicators of dopamine metabolism in the prefrontal cortex, while Phenotropil showed non-selectivity onto both behavioral and neurochemical parameters. Piracetam and Phenotropil failed to affect the cortical and striatal serotonin metabolism in both subpopulations.

Introduction. One of the most promising directions in the search for biologically active compounds is the molecular design of biologically active compounds containing a known pharmacoform fragment. In this article, phenylacetic acid derivatives are considered as a scaffold for the search for biologically active compounds. However, the phenylacetamide derivative is of particular interest, its fragment is included in the structure of the atenolol drug. Optimization of methods for the synthesis of N-acylphenylacetamides and N-acyl-β-ketoamides will expand the boundaries of molecular design and targeted synthesis of biologically active substances containing a phenylacetic acid fragment as a centroid.Aim. Obtain N-acylphenylacetamides and N-acyl-β-ketoamides, optimize the synthesis and isolation methods, and establish the degree of manifestation of the psychotropic activity of the compounds.Materials and methods. Obtaining the target N-acylphenylacetamides was carried out by the interaction of 2-phenylacetamide with carboxylic acid anhydrides under conditions of acid catalysis. The next stage of the synthesis was the preparation of N-acyl-β-ketoamides by the interaction of the synthesized N-acylphenylacetamides with carboxylic acid anhydrides in the proposed catalyst for boron trifluoride diacetate. The structure of the compounds was confirmed by IR, 1H NMR spectrometry. The individuality and purity of the obtained compounds were monitored by thin layer chromatography. The study of the synthesized compounds on the central nervous system was carried out in the tests "Conditioned reflex of passive avoidance – CPAR", "Extrapolation escape (ETI)", "Morris water maze" and "Beam Walking".Results and discussion. As a result of the research, N-acylphenylacetamides and N-acyl-β-ketoamides were synthesized. The essence of the optimization of the procedure for the synthesis of N-acylphenylacetamides is to replace chloric 65 % with concentrated sulfuric acid. The 1H NMR spectra confirming the structures of the synthesized compounds revealed important characteristic features for N-acetyl-3-oxo-2- phenylpentanamide (VI) and N-acetyl-3-oxo-2-phenylhexanamide (VIII) containing a chiral center. The resulting substances have a pronounced effect on the central nervous system, their nootropic activity is to reduce the severity of sensorimotor disorders in animals. As a result of the study, the leading compounds were identified, superior to the effect of the reference drug piracetam.Conclusion. The carried out research confirms the expediency of searching for highly effective and safe nootropic agents in the series of acylated derivatives of phenylacetic acid amide.

Abstract Therapeutically, piracetam has been used for decades as a cognitive enhancer for memory- related neuronal disorders. The present study aimed to investigate the neuroprotective potential of piracetam on lipopolysaccharides (LPS)-induced neuronal deficit using both in-vitro and in-vivo experimental models. For the in-vitro analysis, EOC-20 murine microglial cells were induced with a neuronal toxicity of 100 µg/ml of LPS, and the formation of intracellular reactive oxygen species (ROS) and nitric oxide (NO) productions were determined. For in-vivo neuroprotective analysis, groups of mice were treated orally with two doses of piracetam (200 and 400 mg/kg) for 30 days. Neuronal toxicity was induced by four intraperitoneal injections of LPS (250 µg/kg/day). The malondialdehyde (MDA) level was measured for oxidative stress, and catalase reduced glutathione (GSH), glutathione reductase (GRD), and superoxide dismutase (SOD) levels were determined as the antioxidant parameters. The result of the cell viability study was that pre-treatment with piracetam significantly protected the LPS-induced cell loss, and attenuated the ROS generation and NO production in LPS-induced EOC-20 cells. Moreover, the treatment of piracetam significantly reduced the MDA levels and improved catalase, GSH, GRD, and SOD activities in LPS-induced mice brains. The overall results from this study supported the neuroprotective effects of piracetam against LPS-induced neuronal toxicity.

The aim of this study was to use an alternative granulation technique, solventless roll compaction, and to investigate the effect of the roll compaction pressure on the properties of granules and high-drug-loaded (80%, w/w) immediate release piracetam tablets. Piracetam is commonly manufactured as high drug-loaded tablets by wet granulation with an aqueous binder solution. Due to its high solubility in water, the wet granulation process is largely susceptible to processing methods and can induce the uncontrolled polymorphic transition of piracetam as well as convert it into mono- and di-hydrates. The blends, comprising piracetam, Kollidon® 30, and Avicel® PH-101 were roll compacted at 4, 5 and 13 MPa hydraulic pressure and calibrated using an industrial roll compactor. The resultant granules milled and raw piracetam was investigated with DSC. The resultant granules are mixed with Ac-Di-Sol®, Aerosil® 200 Pharma, and magnesium stearate to prepare tablets using an industrial tablet press at the same compression force and 25, 65, and 100 rpm. The obtained tablets were film coated with an aqueous dispersion of Opadry® II using a pilot-scale solid-wall pan coater. Roll compaction pressure influenced the polymorphic composition of piracetam, the granule properties and tablet mixture in relation to morphology, particle size, flowability, bulk and tapped density, as well as tablet hardness, tablet friability, disintegration, and dissolution. This study showed that roll compaction can be successfully used for the preparation of highly water-soluble, highly drug-loaded piracetam film-coated tablets avoiding wet granulation pitfalls. [ABSTRACT FROM AUTHOR]

The buried interface in inverted perovskite solar cells (PSCs) is critical for determining device performance. However, during annealing, the perovskite crystallized downward from the film's top surfaces, and the use of dimethyl sulfoxide (DMSO) often resulted in voids at the perovskite bottom surface, which negatively impacted PSC performance. In this study, a green solid-state additive, piracetam (PA), was introduced into a perovskite precursor to reduce void formation. Due to the stronger interaction with perovskite components than DMSO, nonvolatile PA could remain within the perovskite films during thermal annealing to avoid volume collapse, thereby preventing the formation of voids at the buried interface as well as passivating the defects of undercoordinated Pb 2+ . Additionally, the introduction of PA could effectively enhance the crystallization of perovskite, leading to an improved quality of the perovskite films and depressed nonradiative recombination. As a result, the power conversion efficiency (PCE) of PSCs increased significantly from 20.95 to 23.42% with excellent operational and thermal stability.

Nootropics, also known as "smart drugs" are a diverse group of medicinal substances whose action improves human thinking, learning, and memory, especially in cases where these functions are impaired. This review provides an up-to-date overview of the potential effectiveness and importance of nootropics. Based on their nature and their effects, this heterogeneous group of drugs has been divided into four subgroups: classical nootropic compounds, substances increasing brain metabolism, cholinergic, and plants and their extracts with nootropic effects. Each subgroup of nootropics contains several main representatives, and for each one, its uses, indications, experimental treatments, dosage, and possible side effects and contraindications are discussed. For the nootropic plant extracts, there is also a brief description of each plant representative, its occurrence, history, and chemical composition of the medicinal part. Lastly, specific recommendations regarding the use of nootropics by both ill and healthy individuals are summarized. [ABSTRACT FROM AUTHOR]

H Introduction: The brain is the target organ for both general anesthetic drugs and some drugs that are used to treat nervous disorders which cause brain activation such as piracetam and citicoline however, they work in contrast to each other. Objective: Our study set out to determine the effect of piracetam and citicoline on the anesthetic induction time. Method: For 10 days 24 mice had been treated with piracetam and citicoline in three groups (piracetam group, citicoline group, and mix group). In addition, 7 mice were used as a control group. All mice were assessed with open field test and underwent right reflex and pain reflex tests. Results: The statistical results showed there is a highly significant relationship between the groups that received drugs in comparison to the control group during assessment by open field test (during the first three sequences) with P-value (0.000, 0.039, 0.008), also a non-significant association relationship between the right reflex test and the drug (piracetam with citicoline). On the other hand, there was a highly significant association relationship between the pain reflex test and the drug (piracetam with citicoline) with P-value(0.009). Conclusion: the time required to achieve the surgical anesthesia stage had been delayed by the influence of piracetam and citicoline use. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits represent an urgent biomedical problem, and are commonly reduced by nootropic drugs. Animal models, including both rodents and zebrafish, offer a valuable tool for studying cognitive phenotypes and screening novel nootropics. Beta-alanine and its derivatives have recently been proposed to exert nootropic activity. Aims: This study aimed to characterize putative nootropic profile of a novel β-alanine analogue, 1,3-diaminopropane (MB-005), in adult zebrafish. Methods: Nootropic profile of MB-005 was assessed in adult zebrafish in the novel tank and conditioned place aversion (CPA) tests acutely, and in cued-learning plus-maze (PMT) tests chronically. Results/Outcomes: MB-005 did not alter zebrafish anxiety-like behavior or monoamine neurochemistry acutely, improved short-term memory in the CPA test, but impaired cognitive performance in both CPA and PMT tests chronically. Conclusions/Interpretation: This study reveals high sensitivity of zebrafish cognitive phenotypes to MB-005, suggesting it as a potential novel cognitive enhancer acutely, but raises concerns over its cognitive (and, possibly, other) side-effects chronically. [ABSTRACT FROM AUTHOR]

N -Phenylacetyl-L-prolylglycine ethyl ester (Noopept, GVS-111, omberacetam) is an orally available active pharmaceutical ingredient (API), with neuroprotective properties and ability to enhance cognitive function. It belongs to nootropic family of drugs and is included in the group of racetams, although its chemical structure is quite different than the other compounds from this group, including the most popular one – piracetam. The mechanism of action of this API is multifaced and is considered to be involving modulation of various neurotransmitter systems within the brain. Despite the significant amount of works devoted to the pharmacodynamics of Noopept, very little is known about its structural and physicochemical properties. Therefore, the aim of current study was to investigate this API in a very thorough way. In this work, the detailed physicochemical analysis of Noopept has been done using TGA/DSC, 1H and 13C liquid state NMR, 13C CP/MAS NMR, SEM, SCXRD, and PXRD. Additionally, quantum chemical DFT computations under periodic boundary conditions, using CASTEP, were conducted to facilitate the analysis of experimental results. Besides, we've performed a polymorphism screening of this molecule. • Detailed physicochemical analysis of Noopept has been performed. • Crystal structure of Noopept was determined using SCXRD. • Polymorph screening has been performed for Noopept. • Periodic DFT calculations were used for analysis NMR and FT-IR spectra of Noopept. [ABSTRACT FROM AUTHOR]

Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs.

[Display omitted] • Piracetam mitigates cisplatin induced nephrotoxicity. • Piracetam improved renal morphology and biochemical parameters of renal function. • Piracetam modulates oxidative stress, inflammation and apoptosis. • Piracetam modulated molecular pathways regulated by AMPK. Cisplatin (CDDP) is commonly employed as an antineoplastic agent, but its use is significantly limited by the occurrence of dose-dependent nephrotoxicity, the detailed mechanisms of which remain unclear. This research is aimed to explore the molecular mechanisms of Piracetam (PIR)'s protective effects on nephrotoxicity resulting from CDDP exposure and to elucidate the mechanisms responsible for these effects. PIR was given in dosages of 100 and 300 mg/kg body weight for a duration of 15 days; concurrently, on the last day, a single 10 mg/kg dose of CDDP was delivered via intraperitoneal injection. Forty-eight hours post-CDDP injection, the animals were sacrificed to assess nephrotoxicity. Blood samples and renal tissues were taken for biochemical and histopathological investigations. Serum creatinine and blood urea nitrogen (BUN) were measured. AMP-activated protein kinase (AMPK), caspase-9 and nuclear factor kappa b p65 (NF-κB p65) were assessed by immunohistochemistry method. Enzyme-linked immunosorbent assay (ELISA) analysis was employed to determine cytochrome c (Cyt. c), Bcl-2-associated X-protein (BAX), caspase-3, nuclear factor erythroid 2–related factor 2 (Nrf2), Heme oxygenase-1 (HO-1), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), myeloperoxidase (MPO), and interleukin-1β (IL-1β) levels in renal tissue homogenates. The mRNA levels of tumor protein P53 (TP53), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinases (JNK) were tested by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, histopathological evaluations of the renal tissues and the binding affinity of PIR to AMPK by molecular docking were also performed. Pre-treatment with PIR enhanced renal function markers such as urea and creatinine, mitigated histological damage, and diminished inflammatory cell presence in renal tubules. PIR demonstrated antioxidant effects by reestablishing the equilibrium between pro-oxidants and antioxidants such as MPO, HO-1, Nrf2, as well as SOD. Furthermore, PIR inhibited the inflammatory pathways through the MAPK/NF-κB pathway. Additionally, PIR counteracted the CDDP-induced decline in PI3K/Akt activity and hindered caspase-dependent apoptotic processes. In summary, PIR appears to be an effective therapeutic strategy for reducing CDDP-induced nephrotoxicity, attributed to its antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Consequently, PIR may serve as a complementary treatment alongside CDDP to alleviate nephrotoxicity associated with CDDP. [ABSTRACT FROM AUTHOR]

[Display omitted] • The encapsulation of piracetam in nonionic micellar system to calculate partition coefficient and binding constant. • Tween 80 and Triton X – 100 are utilized to enhance the solubility and bioavailability of piracetam. • The encapsulation of piracetam in tween 80 micelles is more prominent and more spontaneous. • Mixed micellization is more favorable and effective than single surfactant micellization. Nonionic surfactants have drawn tremendous attention for micellar solubilization, sustained release of the drug, encapsulation of pharmaceutically active ingredients, and permeabilization due to their distinct physicochemical characteristics. Concise solubility investigations are required for the appropriate selection of nonionic surfactant that is to be used for a formulation. In the present research, a cluster of micelles was developed that relies on trapping and stabilizing piracetam by balancing the hydrophilic and hydrophobic forces of nonionic surfactants. Tween 80 and Triton-X 100 and a mixture of these surfactants were used to clarify the drug-surfactant interaction in an aqueous and micellar medium. The interaction was investigated in premicellar, micellar, and post-micellar regions by using UV/Visible spectroscopy. Spectroscopic parameters were calculated to determine the degree of solubilization in terms of the partition coefficient (K x), binding constant (K b), and their respective energies in terms of Gibbs free energy of partition (ΔG p) and Gibbs free energy of binding (ΔG b) for piracetam. The solubilization of piracetam is enhanced by mixing an adequate amount of both nonionic surfactants. The obtained results demonstrated that solubilization is spontaneous and entropically favorable and the cluster of micelles in both single and mixed micellar mediums are stable due to the presence of a much more hydrophobic and hydrophilic culture which provides a synergistic link between the two surfactants. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage. Methods: A randomized controlled trial was used in this study conducted at Baoding First Central Hospital, China from January 2017 to December 2019. Sixty patients with intraventricular hemorrhage were randomly divided into two groups. Patients in the control group were treated with external ventricular drain, while patients in the experimental group were given intraventricular urokinase injection and intravenous piracetam on the basis of the control group. The incidence of adverse drug reactions, hospitalization time, hematoma elimination time, and drainage tube removal time in two groups were compared and analyzed including the cerebrospinal fluid protein content, changes in GCS score, neurological function recovery (ADL score), and Glasgow outcome scale (GOS) of the two groups after treatment. Results: The hematoma elimination time, drainage tube removal time and hospitalization time of the experimental group were shorter than those of the control group, with a statistically significant difference (P<0.05). After treatment, compared with the control group, the protein content of cerebrospinal fluid in the experimental group decreased more significantly (P=0.00), the GCS score was higher (P=0.00), the overall good rate of neurological function was higher (P=0.04), while the rate of good prognosis was higher (P=0.03). Within one month of treatment, the incidence of surgical complications in experimental group was significantly lower than that in control group (P=0.04). Conclusions: External ventricular drain combined with intraventricular urokinase injection and intravenous piracetam is an effective method for the treatment of intraventricular hemorrhage, which is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Cocrystals of 2,7‐dihydroxynaphthalene (DHN, or naphthalene‐2,7‐diol) with isoniazid (pyridine‐4‐carbohydrazide) (INH), denoted DHN–INH [C10H8O2·C6H7N3O, (I)], and piracetam [2‐(2‐oxopyrrolidin‐1‐yl)acetamide] (PIR), denoted DHN–PIR [C10H8O2·C6H10N2O2, (II)], were obtained by the solvent‐assisted grinding method and characterized by IR spectroscopy, powder X‐ray diffraction and single‐crystal X‐ray diffraction. Cocrystal (I) crystallized in the triclinic space group P and showed a 2:2 stoichiometry. DHN and INH molecules are connected by O—H...N(pyridine) and O—H...N(hydrazide) hydrogen bonds. Cocrystal (II) crystallized in the space group Pca21 with a 1:1 stoichiometry. DHN and PIR molecules are connected by O—H...O=C hydrogen bonds. The supramolecular architecture of cocrystal (I) showed interlinked supramolecular tapes; meanwhile, in cocrystal (II), interlinked supramolecular sheets were observed. [ABSTRACT FROM AUTHOR]

Background Promotion of central control of respiration might contribute in minimization of chronic obstructive lung disease disability. Objectives Our study was done to evaluate the effect of oral supplementation of piracetam tablets in low dose (400 mg twice daily) versus high dose (1200 mg twice daily) in patients with chronic obstructive pulmonary disease grade IV with type II respiratory failure, on respiratory parameters (spirometric, respiratory muscle strength, and diaphragmatic echographic measurements; velocity and excursion), in addition to neuropsychiatric parameters (cognitive functions and brain changes with MRI). Patients and methods This randomized controlled study was conducted on 126 patients who were subjected to oral piracetam and classified into group A (42 patients received 800 mg daily for 3 months), group B (44 patients received 2400 mg daily for 3 months) for 3 months, and group C (40 patients) as a control group. Pulmonary evaluation, by spirometry and respiratory muscle study by Pimax, Pemax, Sniff test, and diaphragmatic echography, was conducted in addition to neuropsychiatric evaluation by Alzheimer disease 8 cognitive score assessment and brain MRI. Results Total pulmonary fractional functional progress of piracetam was higher in group B (28.12%) than group A (23.27%) and the control group (5.68%). On the contrary, neuropsychiatric fractional functional progress was higher in group B (29.11%) than group A (15.7%), and lastly, the control group (

Progressive myoclonic epilepsy (PME) is a group of rare diseases characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. PME has high genetic heterogeneity, and more than 40 genes are reportedly associated with this disorder. SEMA6B encodes a member of the semaphorin family and was first reported to cause PME in 2020. Herein, we present a rare case of PME due to a novel SEMA6B gene mutation in a 6-year-old boy born to healthy non-consanguineous Chinese parents. His developmental milestones were delayed, and he developed recurrent atonic seizures and myoclonic seizures without fever at 3 years and 11 months of age. He experienced recurrent myoclonic seizures, non-convulsive status epilepticus (NCSE), atonic seizures, and atypical absence seizures during the last 2 years. At different time points since onset, valproic acid, levetiracetam, piracetam, and clobazam were used to control the intractable seizures. Notably, NCSE was controlled by a combination of piracetam with clobazam and valproic acid instead of intravenous infusion of midazolam and phenobarbital. Due to the limited number of cases reported to date, the clinical description of our case provides a better understanding of the genotype–phenotype correlations associated with PME and indicate that piracetam may be effective against NCSE in patients with SEMA6B-related PME.

A recently identified mechanism for oligomeric Aβ-induced glutamate release from astrocytes involves intracellular Ca elevation, potentially by Ca-dependent vesicular release. Evidence suggests that levetiracetam (LEV; Keppra), an antiepileptic drug, can improve cognitive performance in both humans with mild cognitive impairment and animal models of Alzheimer disease. Because LEV acts by modulating neurotransmitter release from neurons by interaction with synaptic vesicles, we tested the effect of LEV on Aβ-induced astrocytic release of glutamate. We used a fluorescence resonance energy transfer-based glutamate sensor (termed SuperGluSnFR), whose structure is based on the ligand-binding site of glutamate receptors, to monitor glutamate release from primary cultures of human astrocytes exposed to oligomeric amyloid-β peptide 1-42 (Aβ42). We found that LEV (10 µM) inhibited oligomeric Aβ-induced astrocytic glutamate release. In addition, we show that this Aβ-induced glutamate release from astrocytes is sensitive to tetanus neurotoxin, an inhibitor of the vesicle release machinery. Taken together, our evidence suggests that LEV inhibits Aβ-induced vesicular glutamate release from astrocytes and thus may underlie, at least in part, the ability of LEV to reduce hyperexcitability in Alzheimer disease.

Genomics is a disruptive technology, having revealed that cancers are tremendously complex and differ from patient to patient. Therefore, conventional treatment approaches fit poorly with genomic reality. Furthermore, it is likely that this type of complexity will also be observed in other illnesses. Precision medicine has been posited as a way to better target disease-related aberrations, but developing drugs and tailoring therapy to each patient's complicated problem is a major challenge. One solution would be to match patients to existing compounds based on in silico modeling. However, optimization of complex therapy will eventually require designing compounds for patients using computer modeling and just-in-time production, perhaps achievable in the future by three-dimensional (3D) printing. Indeed, 3D printing is potentially transformative by virtue of its ability to rapidly generate almost limitless numbers of objects that previously required manufacturing facilities. Companies are already endeavoring to develop affordable 3D printers for home use. An attractive, but as yet scantily explored, application is to place chemical design and production under digital control. This could be accomplished by utilizing a 3D printer to initiate chemical reactions, and print the reagents and/or the final compounds directly. Of interest, the Food and Drug Administration (FDA) has recently approved a 3D printed drug-levetiracetam-indicated for seizures. Further, it is now increasingly clear that biologic materials-tissues, and eventually organs-can also be "printed." In the near future, it is plausible that high-throughput computing may be deployed to design customized drugs, which will reshape medicine.

A set of thermoanalytical methods and the well-known methodological principle of composition–property relationship were used to find the optimum composition of the caffeine–paracetamol–piracetam model disperse system with preset in vitro pharmaceutical characteristics. The work was aimed at studying phase diagrams of the related condensed system and several technological parameters of the tableted composition form corresponding to an invariant point on the phase (melting) diagram of this system. The thermal properties of the binary component subsystems and then the ternary system itself were studied in air on a DSC-500 differential scanning calorimeter (Russia) in the range 20 – 250°C in heating mode at 10°C/min. Rectangular phase (melting) diagrams of the systems paracetamol–piracetam, caffeine–paracetamol, and caffeine–piracetam were constructed based on the onset temperatures of deviation of the DSC curves from the thermogram baselines of individual compositions. Data on phase equilibria in the caffeine–paracetamol–piracetam ternary system were presented. A eutectic of the ternary system was observed at a component ratio of 8:48:44 mass% (or 3.7:29:67.3 mol%), respectively, with a melting point of 90.6°C. The binary eutectic mixtures related to the ternary system being considered and the ternary eutectic dispersion were shown to differ from mixtures with other ratios of the same series by improved compressibility and release of active components. Tablets obtained from the eutectic dispersions by direct pressing were characterized by increased mechanical abrasion resistance and compression strength under standard test conditions. [ABSTRACT FROM AUTHOR]

Chronic hyperglycemia, insulin resistance, endothelial dysfunction, and disturbance of the integrity of the blood-brain barrier are considered as strategically important links in the development of cognitive deficits in diabetic encephalopathy. Taking this into account, one of the modern trends in the optimization of the treatment of cognitive impairments induced by prolonged hyperglycemia is the co-administration of agents with antihyperglycemic and nootropic activity, in particular, metformin with piracetam. It has been shown that under conditions of experimental alloxan-induced hyperglycemia, piracetam has insufficient nootropic potential for eliminating cognitive deficits. Metformin has a weak nootropic effect in short-term use in low doses, without exhibiting these properties in prolonged administration. When combined with piracetam, metformin potentiates its antiamnesic properties, which helps to restore cognitive functions impaired by hyperglycemia. It is assumed that the mechanisms of such synergism are mediated by a decrease in the content of early and late markers of the destruction of protein molecules, the level of stable nitric oxide metabolites in the cerebral cortex, as well as a significant limitation of the manifestations of ultrastructural destructive changes in hippocampal neurons with a simultaneous improvement in the state of its microvasculature. The obtained results indicate the expediency of the combined use of metformin with nootropic agents for the prevention or treatment of cognitive impairments that occur as a result of diabetes mellitus.

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients., Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months., Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients., Trial Registration: ChiCTR2000040466, date of registration: November 28, 2020., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Piracetam, a widely recognized nootropic drug, is hypothesized to enhance memory function through its influence on synaptic plasticity and neurotransmitter levels. However, despite its popularity, there remains a lack of conclusive evidence regarding its impact on memory. Therefore, the present study aims to explore the effects of piracetam on memory in individuals with impaired cognitive function, comparing it to a placebo control group., Objectives: This study will evaluate how piracetam affects memory function, compared to placebo in adults with impairment in this area., Methods: We carried out bibliographical research and meta-analysis of scientific clinical trials comparing memory function in people taking piracetam with those in the placebo group. The PubMed, Dimensions, Embase, and Cochrane Library databases were used. Statistical analysis was performed in R Studio version 4.3.1., Results: In our analysis, 199 articles were identified, of which we included eighteen studies, comprising a total of 886 patients, of which Piracetam was the treatment option in 442 (49.88 %) patients. Memory enhancement (SMD 0.75; 95 % CI [-0.19; 1.69]; p=0.12; I²=96 %) had no clinical difference between the intervention and the control group., Conclusion: Upon the conclusion of this study, it is apparent that we cannot definitively ascertain the impact of piracetam on memory function. Further research is warranted to provide a clearer understanding of the cognitive effects of piracetam in individuals with memory impairment. This investigation serves as a significant contribution to the ongoing quest to elucidate the potential benefits of piracetam in the field of cognitive neuroscience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)