[Therapeutic effect and mechanism of piracetam for the treatment of spinal cord injury in rats through MAPK pathway].

OBJECTIVE: To explore mechanism of piracetam for the treatment of spinal cord injury in rats through mitogen-activated protein kinase (MAPK) pathway. METHODS: Fifty-four healthy 6-week-old SD female rats with body weight of 80 to 100 g were divided into sham operation group, spinal cord injury group and piracetam group by random number table method, with 18 rats in each group. Spinal cord injury model was established in spinal cord injury group and piracetam group using percussion apparatus, while sham operation group did not damage spinal cord. Piracetam group was injected with piracetam injection through tail vein according to 5 ml·kg-1 standard, once a day for 3 days;the other two groups were injected with normal saline at the same dose, the same frequency and the same duration. The rats were sacrificed at 1, 3, and 7 days after surgery, and changes of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was observed and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect spinal cord inflammatory factors, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1ß (interleukin-1ß), necrosis factor-α (IL-1ß) and tumor necrosis factor-α (TNF-α);HE staining was used to observe morphological changes of rats with spinal cord injury, and immunohistochemistry was used to observe expression level of aquaporin 4 (AQP4). The activation of MAPK signaling pathway in spinal cord of rats after spinal cord injury was observed by western blotting (WB). RESULTS: BBB scores of sham operation group on 1, 3 and 7 day were 21 points. In spinal cord injury group, the scores were (1±1), (4±1) and (7±2);piracetam group was (1±1), (5±1), (9±2), respectively;the difference between spinal cord injury group and sham operation group was statistically significant (P<0.05). HE staining showed that no abnormality was found in sham operation group. In spinal cord injury group, bleeding and degeneration of spinal cord tissue appeared at 1 day after operation; flaky necrotic areas were appeared in spinal cord at 3 days after surgery, and spinal cord tissue began to slowly repair at 7 days after surgery. In piracetam group, the bleeding area was less than that of spinal cord injury group at 1 day after surgery;at 3 days after operation, the necrotic area was reduced and the range of nuclear disappearance was reduced; and the spinal cord began to recover slowly at 7 days after surgery. AQP4 staining of spinal cord of rats in sham operation group was weak at 1, 3 and 7 days after modeling, AQP4 staining was deepened and area increased in spinal cord injury group, AQP4 staining of piracetam group was lighter than that of spinal cord injury group, and the positive cells were slightly increased and the staining was slightly darker than that of sham operation group. At 1, 3 and 7 days, the level of IL-6, IL-10, IL-1ß and TNF-α in spinal cord injury group were higher than those in sham operation group and piracetam group(P<0.05). Compared with spinal cord injury group, the area of spinal cord bleeding and necrosis were decreased by HE staining in piracetam group, and AQP4 staining was decreased by immunohistochemistry. WB results showed that P-ERK, P-JNK and P-P38 levels in spinal cord injury group at 3 days were higher than those in sham operation group and piracetam group(P<0.05). CONCLUSION: Piracetam not only showed significant effect in promoting motor function recovery after spinal cord injury, but also showed positive therapeutic potential in reducing lesion area, regulating AQP4 expression to reduce edema, and reducing inflammatory response by regulating MAPK signaling pathway.

Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K/Akt and MAPK/JNK/ERK signaling pathways.

AIMS: 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. MAIN METHODS: 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-1ß (IL-1ß) 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

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.

Cognitive effects of piracetam in adults with memory impairment: A systematic review and meta-analysis.

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.

Effect of Piracetam and Iron Treatment on Heart Rate Variability in Patients With Breath-Holding Spell.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Development of new nanofibrous nerve conduits by PCL-Chitosan-Hyaluronic acid containing Piracetam-Vitamin B12 for sciatic nerve: A rat model.

Peripheral nerve injury is a critical condition that can disrupt nerve functions. Despite the progress in engineering artificial nerve guidance conduits (NGCs), nerve regeneration remains challenging. Here, we developed new nanofibrous NGCs using polycaprolactone (PCL) and chitosan (CH) containing piracetam (PIR)/vitamin B12(VITB12) with an electrospinning method. The lumen of NGCs was coated by hyaluronic acid (HA) to promote regeneration in sciatic nerve injury. The NGCs were characterized via Scanning Electron Microscopy (SEM), Fourier transform infrared (FTIR), tensile, swelling, contact angle, degradation, and drug release tests. Neuronal precursor cell line (PCL12 cell) and rat mesenchymal stem cells derived from bone marrow (MSCs) were seeded on the nanofibrous conduits. After that, the biocompatibility of the NGCs was evaluated by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, and SEM images. The SEM demonstrated that PCL/CH/PIR/VITB12 NGCs had nonaligned, interconnected, smooth fibers. The mechanical properties of these NGCs were similar to rat sciatic nerve. These conduits had an appropriate swelling and degradation rate. The In Vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VITB12 NGCs towards PC12 cells and MSCs. The in vitro studies exhibited favorable biocompatibility of the PCL/CH/PIR/VIT B12 NGCs towards MSCs and PC12 cells. To analyze functional efficacy, NGCs were implanted into a 10 mm Wistar rat sciatic nerve gap and bridged the proximal and distal stump of the defect. After three months, the results of sciatic functional index (55.3 ± 1.8), hot plate latency test (5.6 ± 0.5 s), gastrocnemius muscle wet weight-loss (38.57 ± 1.6 %) and histopathological examination using hematoxylin-eosin (H&E) /toluidine blue/ Anti-Neurofilament (NF200) staining demonstrated that the produced conduit recovered motor and sensory functions and had comparable nerve regeneration compared to the autograft that can be as the gold standard to bridge the nerve gaps.

The neuroprotective effects of Piracetam on cisplatin-induced cognitive decline.

AIM: This 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. MATERIALS AND METHODS: The study incorporates four groups of mice receiving varied medication regimens, with memory tested using the Novel Location Recognition (NLR) method. RESULTS: 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. LIMITATIONS: 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. CONCLUSIONS: 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.

Effect of organic acids on the solid-state polymorphic phase transformation of piracetam.

Metastable polymorphs are frequently used in oral solid dosage forms to enhance the absorption of poorly water-soluble drug compounds. However, the solid phase transformation from the metastable polymorph to the thermodynamically stable polymorph during manufacturing or storage poses a major challenge for product development and quality control. Here, we report that low-content organic acids can exhibit distinct effects on the solid-state polymorphic phase transformation of piracetam (PCM), a nootropic drug used for memory enhancement. The addition of 1 mol% citric acid (CA) and tricarballylic acid (TA) can significantly inhibit the phase transformation of PCM Form I to Form II, while glutaric acid (GA) and adipic acid (AA) produce a minor effect. A molecular simulation shows that organic acid molecules can adsorb on the crystal surface of PCM Form I, thus slowing the movement of molecules from the metastable form to the stable form. Our study provides deeper insights into the mechanisms of solid-state polymorphic phase transformation of drugs in the presence of additives and facilitates opportunities for controlling the stability of metastable pharmaceuticals.

Docosahexaenoic Acid Plus Piracetam Versus Piracetam Alone for Treatment of Breath-Holding Spells in Children: A Randomized Clinical Trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: DHA plus piracetam is more effective than piracetam alone in decreasing the frequency and severity of BHS in children.

Environmentally sustainable DRS-FTIR probe assisted by chemometric tools for quality control analysis of cinnarizine and piracetam having diverged concentration ranges: Validation, greenness, and whiteness studies.

A novel diffuse reflectance fourier transform infrared spectroscopic method accompanied by chemometrics was optimized to fulfill the white analytical chemistry and green analytical chemistry principles for the quantification of cinnarizine and piracetam for the first time without any prior separation in their challenging pharmaceutical preparation, which has a pretty substantial difference in the concentration of cinnarizine/piracetam (1:16). Furthermore, the suggested method was used for cinnarizine/piracetam dissolution testing as an effective alternative to traditional methods. For the cinnarizine/piracetam dissolution tests, we used a dissolution vessel with 900 mL of phosphate buffer pH 2.5 at 37 °C ± 0.5 °C, then the sampling was carried out by frequent withdrawal of 20 µl samples from the dissolution vessel at a one-minute interval, over one hour, then representative fourier transform infrared spectra were recorded. To create a partial-least-squares regression model, a fractional factorial design with 5 different levels and 2 factors was used. This led to the creation of 25 mixtures, 15 as a calibration set and 10 as a validation set, with varying concentration ranges: 1-75 and 16-1000 µg/mL for cinnarizine/piracetam, respectively. Upon optimization of the partial-least-squares regression model, in terms of latent variables and spectral region, root mean square error of cross-validation of 0.477 and 0.270, for cinnarizine/piracetam respectively, were obtained. The optimized partial-least-squares regression model was further validated, providing good results in terms of recovery% (around 98 to 102 %), root mean square error of prediction (0.436 and 3.329), relative root mean square error of prediction (1.210 and 1.245), bias-corrected mean square error of prediction (0.059 and 0.081), and limit of detection (0.125 and 2.786) for cinnarizine/piracetam respectively. Ultimately, the developed method was assessed for whiteness, greenness, and sustainability using five assessment tools. the developed method achieved a greener national environmental method index and complementary green analytical procedure index quadrants with higher eco-scale assessment scores (91), analytical greenness metric scores (0.87), and red-greenblue 12 algorithm scores (89.7) than the reported methods, showing high practical and environmental acceptance for quality control of cinnarizine/piracetam.

Neuroprotective effect of piracetam-loaded magnetic chitosan nanoparticles against thiacloprid-induced neurotoxicity in albino rats.

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.

Piracetam as a Therapeutic Agent for Doxorubicin-Induced Cognitive Deficits by Enhancing Cholinergic Functions and Reducing Neuronal Inflammation, Apoptosis, and Oxidative Stress in Rats.

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.

Effect of roll compaction pressure on the properties of high drug-loaded piracetam granules and tablets.

OBJECTIVE: 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. SIGNIFICANCE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Nootropics as Cognitive Enhancers: Types, Dosage and Side Effects of Smart Drugs.

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.

Observation on the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage.

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.

Analysis of two mixtures containing racetams in their pharmaceuticals using simple spectrophotometric methodologies.

BACKGROUND: Green spectrophotometric methods were developed and validated for determination of some CNS active drugs as antiepileptics and brain stimulants. OBJECTIVE: Piracetam (PIR), Levetiracetam (LEV) and Brivaracetam (BRV) were assayed as a ternary mixture using double divisor-ratio spectra derivative (DDRSD) (method I). One more binary co-formulated mixture of Piracetam (PIR) and Vincamine (VIN) was assayed using difference spectrophotometric procedures (method II). METHOD: I was applied to determine PIR at 302nm in the first derivative of the ratio spectra in the selected spectral region. The content of LEV was determined by measuring the spectra at 215nm in the first derivative of the ratio spectra in the selected spectral region. The concentration of BRV was estimated by measuring the first derivative of the ratio spectra in the chosen spectral region and detecting the signals at 229.7nm. The application of method (II) procedures resulted in measuring the absorbance of PIR at 220nm which is the zero crossing point on the difference spectra of VIN in 0.1M NaOH vs. 0.1M HCl. Similarly, the absorbance of VIN was measured at 245.0nm, which is the zero crossing point on the difference spectra of PIR. RESULTS: The suggested methods were fully validated adopting ICH guidelines. The linearity ranged from 10-100µg/mL for the three racetams and from 2-20 for VIN. The recovery percentages were ranged from 98.72% to 101.8% for method I and from 98.13% to 101.06% for method II. Moreover, the proposed methods were proved environmentally benign using the most recent assessment tool named AGREE. CONCLUSION: Both procedures were successfully applied for the determination of each drug in bulk powder, checked using laboratory prepared mixtures, and directly applied on commercially available pharmaceutical products without interference. The obtained results revealed a good agreement with those obtained by the reported methods.

Extract of Xylopia aethiopica and its kaurene diterpene, xylopic acid, improve learning and memory in mice.

Background: Cognitive dysfunction, presenting as learning and memory impairment, is a common manifestation in many chronic diseases of the nervous system. Some of these diseases include depression, epilepsy, and Alzheimer's disease. To date, few drugs or medicinal products have shown ability to improve learning and memory deficits. Neuroprotection is one of the mechanisms by which memory could be improved. The extract of Xylopia aethiopica and its kaurene derivative, xylopic acid, have previously demonstrated neuroprotective effects in animal models. The aim of the present study was to investigate the effect of an extract of Xylopia aethiopica fruit and xylopic acid, on learning and memory using murine models. Materials and methods: Unripe Xylopia aethiopica fruits were collected, dried, and extracted using 70% v/v ethanol. Xylopic acid was isolated from the fruits using petroleum ether, concentrated with ethyl acetate and then recrystallized with petroleum ether before purifying with ethanol (96%v/v). Institute of Cancer Research (ICR) mice received oral doses of the extract of Xylopia aethiopica (XAE; 30, 100 and 300 mg/kg), xylopic acid (XA; 30, 100 and mg/kg), citicoline (300 mg/kg), piracetam (300 mg/kg) or ketamine (30 mg/kg) and saline (vehicle). The animals were then taken through the Morris water maze test (MWM), spontaneous alternation Y-maze test (Y-maze), and novel object recognition test (NOR), to assess learning and memory. Results: In the NOR test, XAE (30, 100 and 300 mg/kg) and XA (30, 100 and 300 mg/kg) increased the percentage exploration and recognition index (p = 0.0005 and p < 0.0001, respectively) when compared to both vehicle and ketamine groups. Similarly, doses of XAE and XA as used in the NOR test increased the percentage alternation in the Y-maze test. Although XAE and XA treatments decreased the latencies to find hidden platform in the MWM test, it was not significantly different from the vehicle group. However, this decrease in latency differed significantly when compared to the ketamine group. Interestingly, both XAE and XA treatments increased the percentage frequency to the target quadrant in the probe trial of the MWM. It is noteworthy that in all the three models used, both the extract and xylopic acid performed better than piracetam and citicoline, the reference drugs. Conclusion: The ethanolic extract of Xylopia aethiopica fruit and xylopic acid improved exploratory learning and recognition memory, spatial working, recognition, and reference memories in the behavioral tests.

Pharmacological characterization of a novel putative nootropic beta-alanine derivative, MB-005, in adult zebrafish.

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 ß-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.

Non-convulsive Status Epilepticus in SEMA6B-Related Progressive Myoclonic Epilepsy: A Case Report With Literature Review.

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.

Crystal structures of cocrystals of 2,7-dihydroxynaphthalene with isoniazid and piracetam.

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-1 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.