Doxorubicin (DOXO) is a highly efficient antineoplastic agent, but its clinical usefulness faces major cardiotoxic hazards. Thus, current study aimed to investigate the novel potential ameliorative effect of piracetam (PIRA) against DOXO-induced cardiotoxicity in addition to highlight the role of toll-like receptor 2 (TLR2)/myeloid differentiation primary response 88 (MyD88)/activator protein-1 (AP-1)/nuclear factor kappa-B (NF-κB) and vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling cascades. Rats were allocated in a random manner into five equal groups as follows: control (CONT), PIRA.400, DOXO, DOXO+PIRA.400, and DOXO+PIRA.400 + Nω-nitro-L-arginine methylester (L-NAME). Different cardiac enzymes along with oxidative stress, inflammatory and apoptotic biomarkers were detected. Furthermore, examination of the histopathological alterations in the cardiac tissue was evaluated. DOXO administration remarkably elevated the levels of cardiac enzymes, heart/body weight ratio (%), malondialdehyde (MDA), and upregulated active caspase-3, TLR2/MyD88/AP-1/NF-κB signaling cascade but downregulated VEGF/eNOS pathway along with substantial histopathological alterations. However, levels of serum total antioxidant capacity (T-AOC) and tissue reduced glutathione (GSH) significantly diminished with DOXO administration. All biochemical, histological, and molecular changes were considerably alleviated by the PIRA.400 treatment relative to DOXO alone. Interestingly, findings detected reducing the cardioprotective impact of PIRA on concurrent pretreatment with L-NAME, indicating the crucial role of eNOS in modulating this protection. This study revealed that PIRA ameliorated the DOXO-evoked cardiotoxicity via modulation of TLR2/MyD88/AP-1/NF-κB as well as VEGF/eNOS signaling cascades.

Piracetam (PRM) is a nootropic commonly used to improve cognitive function, memory, and learning ability. This method introduces a new spectrofluorimetric strategy for the identification of PRM, using metal oxide nanomaterials from Shilajit extract in a micellar medium. The technique is based on a unique fluorescent platform of aluminum oxide and nickel oxide nanoparticles (NPs) combined with sodium dodecyl sulfate (SDS). The metal oxide NPs were prepared by an environmentally friendly synthesis approach, using Shilajit extract as a dual‐function agent for reduction and stabilization. Their morphology, size, and structural properties were comprehensively analyzed using a range of spectroscopic and microscopic methods. The innovative technique utilizes the unique fluorescence properties of alumina and NiO NPs in the presence of SDS to detect PRM with remarkable sensitivity and selectivity. This method enables high‐precision measurements over a wide calibration range of 0.5–10 and 0.2–14 μg/mL for the two metal oxides, respectively. With PRM recoveries of 99.07% ± 0.65% and 99.60% ± 0.37%, the method has excellent accuracy and reliability. Medium precision was used to ensure that the method meets stringent precision standards. In addition, the environmentally friendly approach of using Shilajit extract for the sustainable synthesis of metal oxides reduces the impact on the environment while maintaining excellent analytical performance, as confirmed by an environmental impact assessment.

Alzheimer's disease (AD) is an incurable neurological disorder and the primary cause of dementia globally, yet therapeutic options remain limited by poor drug efficacy, low patient adherence, and the restrictive blood-brain barrier (BBB), which prevents over 98% of small molecules from reaching the brain. Piracetam (PIRA), a nootropic agent, and cannabidiol (CBD), a neuroprotective compound, have shown potential in addressing AD-related oxidative stress, inflammation, and neurotransmitter imbalance. However, both drugs exhibit short plasma half-lives, requiring frequent dosing that may reduce patient compliance. To address these challenges, we developed a sustained-release phospholipid phase-transition gel (PPTG) depot incorporating a PIRA-CBD nanoemulsion. A combination index study demonstrated potent synergy at a 1:5 CBD: PIRA ratio. Optimization of the nanoemulsion was carried out using a Box-Behnken design, which explored oil concentration (Capryol® 90), Smix (Tween 20: Cremophor ELP), and stirring speed as key variables. A mean particle size of 137.8nm, a PDI of 0.155, and a zeta potential of -7.587 mV were all observed in the formulation that was optimized. Upon subcutaneous injection, the PPTG showed excellent injectability and formed a stable depot in vivo, as confirmed by gamma scintigraphy. In vitro studies revealed sustained release of 90.538 ± 2.62% PIRA and 87.202 ± 2.16% CBD over 96h, compared to rapid release from the drug solution. This study introduces a novel phospholipid-based phase-transition gel depot incorporating PIRA-CBD nanoemulsion, which provides sustained, targeted brain delivery to enhance therapeutic efficacy and improve patient compliance in Alzheimer's disease management.

Abstract Cognitive and cerebrovascular disorders, such as dementia, Alzheimer's disease, and ischemic stroke, present significant global health challenges, particularly in aging populations. These conditions are characterized by cognitive decline and reduced cerebral blood flow, necessitating therapeutic strategies that address both aspects. Piracetam (PCM), a nootropic agent, enhances memory, learning, and neuroprotection. Vincamine (VCM), a cerebral vasodilator, improves blood flow and oxygen utilization. Their combination offers a synergistic approach to managing dementia impairment with vascular insufficiency. We evaluated RP-HPLC using AGREEprep and ComplexGAPI. PCM and VCM were measured concurrently in pharmaceutical formulations using RP-HPLC to ensure quality, safety, and efficacy. The process offered excellent linearity over a concentration range of 3–50 μg mL−1 for each drug, with coefficients of determination (R2) of 0.999. High sensitivity was achieved, with limits of detection (LOD) of 0.93 μg mL−1 for VCM and 0.32 μg mL−1 for PCM, and limits of quantitation (LOQ) of 2.81 μg mL−1 and 0.90 μg mL−1. Accuracy studies revealed recoveries close to 100% for both drugs, with intra-day and inter-day precision showing RSD ≤2. System suitability parameters met pharmacopeial standards. Dissolution testing in media at pH 1.2, 4.5, and 6.8 revealed pH-dependent release of VCM, with 95.10% dissolution at pH 1.2 and 72% at pH 6.8 after 60 min. In contrast, PCM exhibited rapid and complete dissolution (>95% within 5 min) across all pH levels, consistent with its high solubility. These results validate the method as reliable for quality control and dissolution testing. This supports the development of this promising combination for cognitive and cerebrovascular disorders.

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD50 > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations.

Epilepsy is a chronic neurological disease that affects the brain and causes a recurrent seizure. This condition affects a lot of people worldwide making it a global neurological disorder. The first line for managing epilepsy, is the use of Anti-epileptic drugs. Herein, a reliable and ecological chromatographic method was developed, verified and validated for the simultaneous determination of three approved drugs that can be co-administered in many treatment protocols for epilepsy management; Piracetam (PIR), Gabapentin (GBP) and Levetiracetam (LEV). The developed method was founded on high performance liquid chromatography (HPLC–UV). Separation was accomplished using a 5.0 μm particle size, 250 × 4.6 mm Inertsil ODS-3 C18 column with the UV detection set at 210.0 nm. An isocratic elution system was employed, consisting of a mixture of methanol and water in a ratio of 15:85 (v/v) at ambient temperature. The developed method demonstrated linearity throughout a range of concentration of 30.0–1000.0 µg/mL for GBP and 10.0–100.0 µg/mL for LEV and PIR. The suggested method was optimized and validated following the guidelines stated by the ICH and was utilized for the determination of the aforementioned drugs in their respective pharmaceutical formulation. Moreover, the supremacy of the developed method was further extended for monitoring the in-vitro release profile of the stated drugs and content uniformity of their marketed pharmaceutical formulations. Finally, the ecological impact of the suggested method was monitored, evaluated and compared to the official HPLC ones utilizing newly introduced greenness, blueness and whiteness assessment methods tools.

Valproic acid (VPA) is a very effective therapy used to treat generalized epilepsy, but it must be avoided during pregnancy as it leads to a high risk of teratogenesis. Its teratogenic effect is believed to be due to its placental toxic effect, altering angiogenesis and inducing oxidative stress. Piracetam (PIRA) is a derivative of the neurotransmitter γ-aminobutyric acid (GABA) and has anti-oxidative and pro-angiogenic features. However, its effects against Valproic acid-evoked placental toxicity and abnormal fetal development have not been mechanistically examined. Herein, the present study targets angiogenesis and oxidative stress by Piracetam to investigate the potential modulation of Valproic acid-induced placental toxicity and abnormal fetal development in rats. After administration of Valproic acid (500 mg/kg/day, orally) and/or piracetam (500 mg/kg/day, orally) from the 6th to 15th of gestation, fetuses and placenta were obtained for analysis. The present findings revealed that Piracetam improved the histopathological lesions in the placenta and restored the labyrinth zone area percent. Moreover, it improved the intra-uterine growth retardation (IUGR) via restoring fetal body weight and length and also ameliorated all external malformations (subcutaneous hemorrhage, fore limb, and hind limb anomalies) and additionally amended the skeletal lack of ossification. These favorable effects of Piracetam were mediated by the enhancement of placental angiogenesis via the VEGF/eNOS/TGF-β pathway and attenuating placental oxidative stress, which appeared as decreased MDA content and increased GSH and TAC levels. In conclusion, activation of placental angiogenesis via the VEGF/eNOS/TGF-β axis alongside inhibition of oxidative stress by Piracetam can ameliorate Valproic acid-evoked placental toxicity and, subsequently, fetal malformations in rats.

Metastable polymorphs of active pharmaceutical ingredients can occasionally be used to enhance bioavailability or make processing more convenient. However, the thermodynamic instability of metastable polymorphs poses a severe threat to the quality and performance of the drug products. In this study, we used hot-stage microscopy and powder X-ray diffraction to quantitatively analyze the kinetics of the solid-solid phase transition of piracetam (PCM) polymorphs in the absence and presence of several polymeric excipients. The Forms I and II of PCM are enantiotropically related polymorphs, and the transition point is 75 °C. We found that 1 wt % polymer can strongly affect the transformation rate of Form II to Form I of PCM above 75 °C. PVP K30 has the highest Tg and the strongest inhibitory effect on the transition, whereas PEG has the lowest Tg and the weakest effect on the transition. Below 75 °C, the addition of 1 wt % PEG can decrease the transformation rate from Form I to Form II of PCM by a few orders of magnitude, whereas no phase transition occurs in the presence of the other investigated polymers. The inhibitory effects of the same concentration of polymers on the kinetics of the solid-solid phase transition of piracetam polymorphs are considerably greater than those on the crystallization of PCM from the amorphous phase, especially at low temperatures. We propose that the low segmental mobility of polymers enriched between the crystalline phases can considerably inhibit the nucleation and growth of the stable form at the interface during the phase transition. Our findings deepen the current understanding of the mechanisms underlying the solid-state phase transition of polymorphic drugs in the presence of polymeric excipients, providing a promising formulation approach for stabilizing the metastable pharmaceutical polymorphs.

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 Pb2+. 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.

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

Cocrystal screening and single-crystal growth remain the primary obstacles in the development of pharmaceutical cocrystals. Here, we present a new approach for cocrystal screening, microspacing in-air sublimation (MAS), to obtain new cocrystals and grow high-quality single crystals of cocrystals within tens of minutes. The method possesses the advantages of strong designable ability of devices, user-friendly control, and compatibility with materials, especially for the thermolabile molecules. A novel drug-drug cocrystal of favipiravir (FPV) with salicylamide (SAA) was first discovered by this method, which shows improved physiochemical properties. Furthermore, this method proved effective in cultivating single crystals of FPV-isonicotinamide (FPV-INIA), FPV-urea, FPV-nicotinamide (FPV-NIA), and FPV-tromethamine (FPV-Tro) cocrystals, and the structures of these cocrystals were determined for the first time. By adjusting the growth temperature and growth distance precisely, we also achieved single crystals of 10 different paracetamol (PCA) cocrystals and piracetam (PIR) cocrystals, which underscores the versatility and efficiency of this method in pharmaceutical cocrystal screening.

In traditional medicine, Ximenia americana (XA) is used to treat mental disorders, and headaches. The current study aimed to show the preventive and biochemical impacts of XA aqueou’s extract on diazepam-induced amnesia. Mice were randomized as follows: distilled water (10 mL/kg); diazepam (3 mg/kg); piracetam (PIR) (150 mg/kg); and XA experimental groups (25, 50 and 75 mg/kg). Mice were then treated in groups, 14 straight days. Radial arm maze (RAM) and T-maze were employed to assess different behaviours 30 min after each treatment. After the test was completed, the brains were isolated for histological and biochemical examinations. The results obtained showed that XA extract seriously (p < 0.001) reversed mistakes in working remembrance in the radial arm maze test contrasted to the normal control factions. In the T-maze test, pretreatment of mice with XA extract seriously (p < 0.001) expanded the time spent in the preferred arm when contrasted to the DZP-only treated faction. The XA-treated DZP groups showed subsequent (p < 0.001) improvement in catalase (CAT) and reduced glutathione (GHS). A diminish in malondialdehyde (MDA) level was observed in brain homogenates of mice treated with the extract contrasted with the DZP- group. These few results regarding the neuroprotective and antioxidant effects of XA extract at least partially demonstrate its empirical use in the treatment of certain pathologies.

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

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

Velvet antler peptide (VAP) is one of the main active ingredients in Velvet antler (VA), and its mechanism in preventing mild cognitive impairment (MCI) needs to be further studied. In this research, rats model with MCI was established, non-targeted metabonomics method was performed. Total 50 wistar rats were divided into: control, model, piracetam (PIR), high- and low-dose VAP groups, and were administered for 18 days. Scopolamine (2 mg/kg) was injected intraperitoneally to establish the MCI rat model. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in rat serum were detected by the enzyme-linked immunosorbent assay (ELISA). The expression of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated death promoter (Bad) and Bcl-2-associated X protein (Bax) in hippocampus of rats were detected by Western blot analysis. The brain and kidney of MCI rats were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) metabolomics technology, and the differences of metabolites and the dynamic changes of metabolic pathway were analyzed based on the results of Principal Component Analysis (PCA) and Orthogonal partial least squares discriminant analysis (OPLS-DA) The correlation analysis of significantly different metabolites was then analyzed by Cluster analysis (CA), and then the differential metabolite pathway enrichment analysis was performed. According to the statistical analysis of univariate and multivariates, the models constructed between the groups are stable and reliable, the variability and separation trend are good, and there are differences in the metabolomes. In results, VAP increased the content of serum SOD, reduced the content of MDA, increased the expression level of Bcl-2 and reduced the expression level of Bad and Bax protein in MCI model rats. The relevant potential markers in the brain and kidney of MCI rats mainly included folic acid, acetyl L-carnitine (ALC), Prostaglandin E1 (PGE1), 3′,5′-cyclic-adenosine-monophosphate (cAMP) and various amino acids. Therefore, VAP could inhibit oxidative stress response, reduce hippocampal neuron apoptosis and protect neurons in MCI rats. Its mechanism may be related to regulating folate and lipid metabolism, cyclic adenosine phosphate energy cycle, amino acid biosynthesis and renal secretion of sex hormones.

Validation of a specific Reversed-Phase HPLC method for the quantification of three racetams; Piracetam, Levetiracetam, and brivaracetam in the presence of Co-administered drugs in their pharmaceuticals; greenness assessment and application to biological fluid and in-vitro dissolution testing

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

Background and Aim: Urinary tract infections (UTIs) are one of the most common infectious diseases. Although UTI is mostly associated with several members of the family of Enterobacteriaceae, Escherichia coli (E. coli) is the most common pathogen among them. This study aims to determine the prevalence and resistance pattern of ESBL producing E. coli isolated from patients with urinary tract infection in Sari, Iran. Methods: From December-2016 to June-2017, a hospital-based cross-sectional work was accompanied, and a total of 200 urine samples were cultured on blood agar and MacConkey agar for the identification of etiologic agents. After detection and confirmation of E. coli isolates, susceptibility testing was assessed using the following antibiotics: cefotaxime, ceftazidime, imipenem, nalidixic acid, cefixime, amikacin, ofloxacin, ceftriaxone, cefepime, gentamicin, tobramycin, meropenem, piracetam, and ciprofloxacin with Kirby–Bauer disk-diffusion technique according to the CLSI guidelines. Double-disk synergy (DDS) methods were used for the detection of ESBL-producing strains. Results: In the current study, 120 urinary isolates of E. coli were detected, which ESBL-producing phenotypes were detected in 55% (n = 66) of the isolates. ESBL producing strains of E. coli showed the highest susceptibility to meropenem (100%) and ofloxacin (96%); and showed the highest rates of resistance to ceftazidime (91%), cefepime (87%), cefotaxime, and ceftriaxone (84%). Conclusion: Markedly high resistance to third-generation cephalosporins among E. coli strains was found in the current study. Considering the high prevalence of resistance to third-generation cephalosporins in infections caused by organisms producing ESBL, performing comprehensive tests before prescribing antibiotics is essential for the management of infections caused by these strains in community/hospital-acquired UTIs. Furthermore accompanying molecular-based works on ESBL variants will assistance to achieve better results. *Corresponding Author: Mehrdad Gholami; Email: me.gholami@mazums.ac.ir Please cite this article as: Ahanjan M, Salehian M, Gholami M. Prevalence and Resistance Pattern of Extended-Spectrum β-Lactamase Producing Escherichia coli Isolated from Patients with Urinary Tract Infection. Arch Med Lab Sci. 2020;6:1-7 (e13). https://doi.org/10.22037/amls.v6.33081

Objective To investigate the effect of piracetam combined with fluoxetine on daily living ability of elderly patients with cognitive dysfunction after stroke. Methods A total of 112 elderly patients with cognitive impairment after stroke in Xinzhou People’s Hospital from April 2017 to February 2018 were divided into two groups according to the random number table method, with 56 cases in each group. The reference group was treated with piracetam, and the study group was treated with piracetam and fluoxetine, and the levels of Activity of Daily Living Scale (ADL) were compared between the two groups. Results After 3 months of treatment, the degree of cognitive impairment in the reference group was higher than that in the study group (P 0.05). After 3 months of treatment, the ADL score of the reference group was lower than that of the study group (P 0.05). After 3 months of treatment, the level of BNDF in the reference group was lower than that of the study group (P<0.05). Conclusions The combined treatment of piracetam and fluoxetine for patients with cognitive impairment after cerebral apoplexy can effectively alleviate the degree of cognitive impairment, improve the daily living ability and regulate the level of serum BDNF. Key words: Elderly stroke; Piracetam; Fluoxetine; Cognitive impairment

Advanced Glycation End-Products (AGEs) are created in the last step of protein glycation and can be a factor in aging and in the development or worsening of many degenerative diseases (diabetes, chronic kidney disease, atherosclerosis, Alzheimer’s disease, etc.). Albumin is the most susceptible to glycation plasma protein. Modified albumin by AGEs may be more resistant to enzymatic degradation, which further increases the local accumulation of AGEs in tissues. The aim of the present study was to analyze in vitro glycation of serum albumin in the presence of piracetam (PIR) and the gliclazide (GLZ)-glycated albumin interaction. The analysis of PIR as an inhibitor and GLZ interaction with nonglycated human albumin (HSA) and glycated by fructose human albumin (gHSAFRC), in the absence and presence of piracetam (gHSAFRC-PIR), was performed by fluorescence quenching of macromolecules. On the basis of obtained data we concluded that under the influence of glycation, association constant () of gliclazide to human serum albumin decreases and GLZ binds to HSA with less strength than under physiological conditions. PIR strongly inhibited the formation of AGEs in the system where the efficiency of HSA glycation was the largest. The analysis of piracetam influence on the GLZ-glycated albumin interaction has shown that piracetam increases the binding strength of GLZ to glycated albumin and weakens its therapeutic effect. Based on the obtained data we concluded that monitoring therapy and precautions are required in the treatment when the combinations of gliclazide and piracetam are used at the same time.