Concentrations Of Chlorpromazine Research Articles

Photopolymerization of Chlorpromazine-Loaded Gelatin Methacryloyl Hydrogels: Characterization and Antimicrobial Applications.

This study investigates the synthesis, characterization, and antimicrobial properties of hydrogels synthesized through the UV-pulsed laser photopolymerization of a polymer-photoinitiator-chlorpromazine mixture. Chlorpromazine was used for its known enhanced antimicrobial properties when exposed to UV laser radiation. The hydrogel was formed from a mixture containing 0.05% Irgacure 2959, 10% gelatin methacryloyl, and various concentrations of chlorpromazine (1, 2, and 4 mg/mL). Laser-induced fluorescence spectroscopy was employed to monitor the photoinduced changes of chlorpromazine and Irgacure 2959 during hydrogel formation, providing insight into the photodegradation dynamics. FTIR spectroscopy confirmed the incorporation of irradiated chlorpromazine within the hydrogel matrix, while the release profiles of chlorpromazine showed sustained release only in hydrogels containing 1 mg/mL of CPZ. The hydrogel showed significant antimicrobial activity against MRSA bacteria when compared to that of penicillin. These findings highlight the potential of CPZ loaded during the photopolymerization process into hydrogels as effective antimicrobial agents with sustained release properties, making them suitable for combating resistant bacterial strains.

Electrochemical oxidation of Fe (II) using chlorpromazine drug at boron-doped diamond electrode: application to in vivo mechanism study interaction of chlorpromazine on hemoglobin iron and evaluation of some biomolecules

In this study, the electrochemical properties of aqueous chlorpromazine hydrochloride (CPZ) in the presence of Fe (II) were investigated by cyclic voltammetry at a boron-doped diamond (BDD) electrode. The results showed that an EC′ reaction mechanism occurs, where electrochemically generated CPZ species (cation radical) are reduced by Fe (II) back to the parent CPZ, and Fe (II) is oxidized to Fe (III). The detection limit, sensitivity, and dynamic concentration ranges were 2.8 μM, 0.0188 μA μM−1 and 10–166 μM. Based on the electrochemical results, the interaction of chlorpromazine (CPZ), a widely used antipsychotic tranquillizer, with the allosteric protein, hemoglobin, has been studied. First, four groups of six female rats weighing 400–450 g were selected. The rats were injected with different concentrations of chlorpromazine over a 3-week period, and the concentrations of hemoglobin, methemoglobin, red blood cells (RBCs), and hematocrit (HCT) were analyzed in the blood of each rat. After injection of different concentrations of the drug, the amount of hemoglobin) as a source of Fe (II)) decreased, but the amount of methemoglobin (as a source of Fe (III) increased. In addition, UV spectroscopic measurements in the range of 200–700 nm indicate the conversion of hemoglobin to methemoglobin in chlorpromazine-treated rats compared to the normal sample, and there was a direct relationship between the increasing methemoglobin concentration of chlorpromazine. Furthermore, the amount of RBC and HCT was measured. The results showed that RBC (21.05%–56.52%) and HCT (10.04%–53.19%) decreased. Finally, this study demonstrates a new mechanism for the effects of CPZ on hemoglobin iron in rat blood based on electrochemical results.

Electrochemical Behaviour and Sensing of Chlorpromazine at Polymer‐Free Kaolin‐Based Nanosodalite and Nanosodalite‐Graphene Foam Film modified Glassy Carbon Electrodes

AbstractA nanosodalite (SOD) was synthesized utilizing Cameroonian kaolin and then used to prepare a nanocomposite (SOD‐GF) with graphene foam (GF). The as‐synthesized materials were characterized using X‐ray diffractometry (XRD), Fourier transform‐infrared (FT‐IR) spectroscopy, N2 adsorption‐desorption and scanning electron microscopy coupled with emission dispersive X‐ray (SEM/EDX). The results show a pure sodalite with high degree of crystallinity with crystallite size and BET surface area of 38.3 nm and 22 m2/g, respectively. The composite's characterization revealed a well‐integrated material in which the structural integrity of each material is maintained, its surface area being 4‐fold that of pristine SOD. Stable SOD and SOD‐GF modified glassy carbon electrode (GCE) were prepared by drop coating without a binder and utilized to study the electrochemistry of chlorpromazine (CPZ) in acidic, neutral and basic pHs. It appeared that (i) CPZ's electrochemical oxidation was a two‐step one‐electron process at SOD/GCE and a one‐step two‐electron process at SOD‐GF/GCE and (ii) the electrochemical reaction mechanism was an EEC mechanism at SOD/GCE while at SOD‐GF/GCE the mechanism was EEC at pH<4 and EC for greater pH. SOD/GCE and SOD‐GF/GCE were used to sense CPZ within CPZ's concentration ranging from 0.5‐30 μM with low detection limits.

Nanoarchitectonics of on–off ratiometric signal amplified electrochemical sensor for chlorpromazine with molecularly imprinted polymer based on Ni-MOF/Fe-MOF-5 hybrid Au nanoparticles

A novel and stable on–off ratiometric electrochemical sensing platform for chlorpromazine (CPZ) detection by combing the selective recognition of molecularly imprinted polymer (MIP) technology and ratiometric quantification strategy. Gold nanoparticles (AuNPs) were first electrodeposited on a bare glassy carbon electrode surface and then modified with a mixture of Ni-MOF/Fe-MOF-5 by drop-coating, and subsequently electropolymerization polythionine (pTHi) as an internal reference to achieve a ratiometric on–off response. The reference signal of pTHi was obtained by the boiling water-bath-assisted in-situ electropolymerization method for the first time. Ni-MOF/Fe-MOF-5 hybrid AuNPs (Ni-MOF/Fe-MOF-5/AuNPs) not only benefited the output signal amplification, but also provided the enlarged surface for immobilization of pThi and MIPs, and served as catalytic active centers to oxidation CPZ. Then, the MIPs membrane was fabricated through in-situ electropolymerization by using CPZ as the template molecule, nicotinamide as a functional monomer. Ratiometric identifying and quantitative sensing model has been proposed based on the combination of MIP membrane as molecular recognition receptor and pTHi used as an internal reference probe, which improves the sensitivity and selectivity of the sensor. Under the optimal conditions, the ratiometric signals of peak current (ICPZ/IpTHi) were linear to CPZ concentration in the range of 0.001–40 μM and 40–900 μM, with the ultralow detection limit of 0.025 μM (S/N = 3). Furthermore, this sensor exhibited high anti-interference ability, reproducibility, satisfactory stability, and outstanding measurement performance in biological samples with favorable recoveries in the range of 98.11–100.81%. Together, the constructed on–off ratiometric MIP sensing platform is a promising tool for the rapid and accurate determination of antipsychotic drugs with high selectivity and stability.

Expression Analysis of Exosomal MicroRNAs in Chlorpromazine Treated Human Hepatic Spheroids: A Promising Tool for Novel Drug-Induced Liver Injury Biomarker Discovery

Introduction: Risk management and mitigation of new drug candidates that induce drug-induced liver injury (DILI) in the clinic is a pivotal task to protect patients and save money during the drug development process. Nevertheless, clinical DILI risk assessment with conventionally available liver biomarkers comes with high failure rates. MicroRNAs (miRNAs) are short noncoding RNA molecules known to regulate mRNA expression. Actively secreted miRNAs which are circulating in patient blood can provide important pathway information involving specific DILI-inducing mechanisms and, therefore, have potential as early diagnostic biomarkers. Materials and Methods: In this study, the exosomal miRNA response of human primary hepatic spheroids treated with toxic concentrations of Chlorpromazine for 3 or 8 days was analyzed. The miRNA response of the hepatic spheroids was analyzed by quantifying a total of 752 miRNAs in the culture medium by quantitative polymerase chain reaction. Results: Clustering and pathway enrichment analysis of the miRNA response revealed several differentially expressed miRNAs involved in the regulation of signaling pathways that are toxicologically relevant, including apoptosis. This exosomal miRNA response was validated by a caspase 3/7 activity assay which confirmed an induction of apoptosis in hepatic spheroids treated with Chlorpromazine. Conclusion: Our results suggest that human hepatic spheroids are a promising test system for the discovery of secreted miRNA signatures. This could become a novel tool for discovery of human in vivo relevant compound-specific DILI biomarkers, inducing understanding mechanisms. In addition, miRNA biomarkers which can be monitored directly in the patient blood can become valuable tools to assist clinicians in risk management.

Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii.

Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.

Caveolae-dependent endocytosis mediates the cellular uptake of CdTe quantum dots in ovarian cancer cell lines.

Quantum dots (QDs) are semiconductor nanocrystals that are widely used in biology due to their good optical properties. QDs, especially cadmium-based QDs, play an important role in the diagnosis and treatment of cancer due to their intrinsic fluorescence. The aim of the present study was the evaluation of the cellular uptake mechanisms of CdTe QDs in ovarian cancer cell lines. In this study, we used CdTe QDs coated with thioglycolic acid. The ovarian cancer cell lines SKOV3 and OVCAR3 were treated with different concentrations of QDs, triamterene, chlorpromazine, and nystatin, and cell viability was evaluated through the MTT test. To find the way of cellular uptake of CdTe QDs, we used the MTT test and interfering compounds in endocytic pathways. Intrinsic fluorescence and cellular internalization of CdTe QDs were assessed using flow cytometry and fluorescence microscopy imaging. The viability of CdTe QDs-treated cells dose-dependently decreased in comparison to untreated cells. To evaluate the cellular uptake pathways of CdTe QDs, in most cases, a significant difference was observed when the cells were pretreated with nystatin. The results of flow cytometry showed the cellular uptake of CdTe QDs was dose- and time-dependent. Nystatin had a measurable effect on the cellular uptake of CdTe QDs. This finding suggests that caveola-mediated endocytosis has a large portion on the internalization of CdTe QDs. According to the results of this study, CdTe QDs may have potential applications in cancer research and diagnosis.

Screening of specific aptamers against chlorpromazine and construction of novel ratiometric fluorescent aptasensor based on metal-organic framework

Chlorpromazine is a phenothiazine representative drug that can be used to anesthetize and calm animals. However, chlorpromazine excess may lead to residual persistence in edible tissues, which is potentially harmful to human health and animal production. In this work, high affinity and specificity aptamers against chlorpromazine were screened out based on Capture-SELEX. After ten rounds of screening, the candidate aptamers were obtained. The optimal aptamer of CHL-3 was obtained by isothermal titration calorimetry (ITC) and SYBR Green I (SGI) fluorescence-competition methods. The Kd value of CHL-3 was 69.8 ± 9.81 nM. Subsequently, the Uio-66-NH2 material was prepared, filled with rhodamine 6G (Rho 6G) dye into the pore, and sealed with CHL-3, and fluorescence probes were obtained. The ratiometric fluorescence detection method was established to detect the concentration of chlorpromazine. A linear relationship was obtained in a range of 1–100 nM, with a lower detection limit of 0.67 nM. Meanwhile, a good recovery was shown in spiked food samples, such as eggs and milk. These results indicate that the constructed ratiometric fluorescence strategy can be successfully applied in food detection.

Comparative Determination of Chlorpromazine in Pharmaceutical Injectable Veterinary and Human Formulations by Spectrophotometric and High Performance Liquid Chromatographic Methods

Background: Chlorpromazine (CPZ) is a phenothiazine tranquilizer used in humans and animals. Rapid determinationof the drug in pharmaceutical preparations is often needed. The aim of the study was to further examine and ascertainasimple spectrophotometric method in comparison with a high performance liquid chromatographic (HPLC) methodfor the determination of CPZ concentrations in injectable pharmaceutical formulations used in man and animals.Methods: Concentrations of CPZ in injectable pharmaceutical formulations for human and veterinary uses weredetermined by a modified spectrophotometric method and by an HPLC method with appropriate standard calibrationcurves. The spectrophotometric method of CPZ determinationwas conducted by diluting 0.1 ml of the veterinary(5%) or 0.3 ml of human (0.5%) formulations to 200 ml of 0.1N sulfuric acid. Four ml of the diluted CPZ samples orthe standard solutions were mixed with 2 ml of 50% sulfuric acid. Then an aliquot of 0.2 ml of 2% ferric nitrate wasadded to the mixture. After 15 minutes, the absorbance was measured at 530 nm against water and vehicle blanksusing a spectrophotometer. The HPLC method applied in the present study consisted of reversed phase gradientchromatography with a C18 column and the eluent was (A) 50 mmol NaH2PO4, pH 2.5 and (B) acetonitrile - 50mmol NaH2PO4, pH 2.5 (60:40 v/v), flow rate at 1 ml/min, with a gradient of 15-55% B in 10 min, to 100% B in20 min, and 280-nm UV detection. From the calibration curves of CPZ standards, the following were calculated:Limit of detection limit (LOD) = 3.3 x SD/slope; Limit of quantitation (LOQ) = 10 x SD/slope, where SD is thestandard deviation of response of CPZ concentrations of the calibration curves.Linear regression analysis and relatedcoefficients of correlations were applied on the calibration curves. Results: The calibration curves of CPZ againstwater or vehicle blanks as determined by the spectrophotometric method or by the HPLC method were linear withstrong correlations (r = and / or >0.99). Based on the calibration curves, limit of detection and limit of quantitation thespectrophotometric method were comparable to those of the HPLC one. The contents CPZ in human and veterinaryinjectable formulations as determined by the spectrophotometricmethod were in accordance (100.6% and 102%,respectively)to the concentrations claimed on the labels of the formulations.Conclusion: The present results introduce a simple spectrophotometric method that could be used for routinemeasurement of CPZ concentrations in pharmaceutical formulations, with the added benefits of linearity, precisionand cost effectiveness.

Kinetics of Crude Peroxidase from the Rind of Watermelon Fruit

Aims: To study the kinetics of crude peroxidase from the rind of watermelon fruit in various assay conditions.
 Study Design: In vitro enzyme assay.
 Place and Duration of Study: Department of Biochemistry, Faculty of Life Sciences, Ambrose Alli University, Ekpoma, Edo State, Nigeria between October 2015 and January 2016.
 Methodology: The activity of the crude peroxidase extracted from the rind of watermelon was determined by measuring the rate of oxidation of KI at 25oC in a 3.0 ml reaction mixture which contained 2.3 ml of 25 mM - 400 mM sodium acetate buffer (pH 3.5-6.0), 0.2 ml of 2 mM KI, 0.1ml of the crude peroxidase, and 0.2 ml of varying concentrations of chlorpromazine (0.01 mM - 0.1 mM). In all cases, 0.2 ml of 0.01 mM – 1 mM H2O2 was added last to initiate the reaction. Only one parameter was varied per assay. Assays were done in five replicates. The initial velocity of the crude peroxidase for KI oxidation was determined using the absorbance at 353 nm.
 Results: The concentration of H2O2 that generated an optimal activity for the crude peroxidase extracted was 0.2 mM, while a pH of 5.5 was optimal for the crude enzyme. The activity of the crude enzyme increased proportionately within a buffer concentration range of 25 mM and 400 mM. Chlorpromazine (0.01 mM - 0.1 mM) proportionately increased the enzyme activity, while promethazine within a range of 0.01 mM and 0.06 mM proportionally increased the enzyme activity. Further increase in promethazine concentration beyond 0.6 mM resulted in a decreased activity of the enzyme.
 Conclusion: This study suggests that the Rind of watermelon is an alternative source of peroxidase. The activity of this peroxidase can be enhanced by high buffer concentrations in the presence of some redox mediators like promethazine and chlorpromazine at a pH of 5.5.

Anti-Plasmid Activity of Chlorpromazine in Types of Antibiotics Resistant Pathogenic Bacteria

This study was performed to evaluate the ability of chlorpromazine compound to cure the plasmids and remove the antibiotic resistance character of multidrug resistance Gram-negative pathogenic bacteria.
 The curing experiment was done by incubating bacterial strains in nutrient broth with sub MIC concentration of chlorpromazine, and the disc diffusion method was used before and after curing to evaluate antibiotic resistance pattern of bacteria. Synergetic test of chlorpromazine with antibiotics that the studied bacteria showed resistance toward also done.
 The results showed the ability of chlorpromazine to remove the plasmids from four bacterial genera out of five genera, where the most plasmid removal cases was with E.cloacae, P.aeruginosa, and P.merabilis, and the loss of antibiotics resistance was observed in the same bacterial genera, but P.merabilis showed the most antibiotics resistance losing by three antibiotics out of nine antibiotics that the bacteria were resistant to them before curing. As for the synergistic effect, the compound showed a synergism with only two antibiotic and with the three aforementioned bacterial genera.
 From results of this study we concluded the possibility of removing bacteria resistance to antibiotics by eliminating plasmids through using chlorpromazine, and the possibility of using this compound in synergism with antibiotics, this will open the way to find new strategies to treat many diseases caused by resistant bacteria.

Inhibition of the replication of SARS-CoV-2 in human cells by the FDA-approved drug chlorpromazine

IntroductionUrgent action is needed to fight the ongoing coronavirus disease 2019 (COVID-19) pandemic by reducing the number of infected cases, contagiousness and severity. Chlorpromazine (CPZ), an antipsychotic from the phenothiazine group, is known to inhibit clathrin-mediated endocytosis and has antiviral activity against severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus. The aim of this in-vitro study was to test CPZ against SARS-CoV-2 in monkey and human cells.Materials and methodsMonkey VeroE6 cells and human alveolar basal epithelial A549-ACE2 cells were infected with SARS-CoV-2 in the presence of various concentrations of CPZ. Supernatants were harvested at day 2 and analysed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for the presence of SARS-CoV-2 RNA. Cell viability was assessed in non-infected cells.ResultsCPZ was found to have antiviral activity against SARS-CoV-2 in monkey VeroE6 cells, with a half maximal inhibitory concentration (IC50) of 8.2 µM, half maximal cytotoxic concentration (CC50) of 13.5 µM, and selectivity index (SI) of 1.65. In human A549-ACE2 cells, CPZ was also found to have anti-SARS-CoV-2 activity, with IC50 of 11.3 µM, CC50 of 23.1 µM and SI of 2.04.DiscussionAlthough the measured SI values are low, the IC50 values measured in vitro may translate to CPZ dosages used in routine clinical practice because of the high biodistribution of CPZ in lungs and saliva. Also, the distribution of CPZ in brain could be of interest for treating or preventing neurological and psychiatric forms of COVID-19.ConclusionsThese preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19.

Repositionnement de la chlorpromazine dans le traitement du COVID-19 : étude reCoVery

ObjectivesThe ongoing COVID-19 pandemic comprises a total of more than 2,350,000 cases and 160,000 deaths. The interest in anti-coronavirus drug development has been limited so far and effective methods to prevent or treat coronavirus infections in humans are still lacking. Urgent action is needed to fight this fatal coronavirus infection by reducing the number of infected people along with the infection contagiousness and severity. Since the beginning of the COVID-19 outbreak several weeks ago, we observe in GHU PARIS Psychiatrie & Neurosciences (Sainte-Anne hospital, Paris, France) a lower prevalence of symptomatic and severe forms of COVID-19 infections in psychiatric patients (∼4%) compared to health care professionals (∼14%). Similar observations have been noted in other psychiatric units in France and abroad. Our hypothesis is that psychiatric patients could be protected from severe forms of COVID-19 by their psychotropic treatments. Chlorpromazine (CPZ) is a phenothiazine derivative widely used in clinical routine in the treatment of acute and chronic psychoses. This first antipsychotic medication has been discovered in 1952 by Jean Delay and Pierre Deniker at Sainte-Anne hospital. In addition, to its antipsychotic effects, several in vitro studies have also demonstrated a CPZ antiviral activity via the inhibition of clathrin-mediated endocytosis. Recently, independent studies revealed that CPZ is an anti-MERS-CoV and an anti-SARS-CoV-1 drug. In comparison to other antiviral drugs, the main advantages of CPZ lie in its biodistribution: (i) preclinical and clinical studies have reported a high CPZ concentration in the lungs (20–200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (30–100 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms of COVID-19. MethodsOur hypothesis is that CPZ could decrease the unfavorable evolution of COVID-19 infection in oxygen-requiring patients without the need for intensive care, but also reduce the contagiousness of SARS-CoV-2. At this end, we designed a pilot, phase III, multicenter, single blind, randomized controlled clinical trial. Efficacy of CPZ will be assessed according to clinical, biological and radiological criteria. The main objective is to demonstrate a shorter time to response (TTR) to treatment in the CPZ+standard-of-care (CPZ+SOC) group, compared to the SOC group. Response to treatment is defined by a reduction of at least one level of severity on the WHO-Ordinal Scale for Clinical Improvement (WHO-OSCI). The secondary objectives are to demonstrate in the CPZ+SOC group, compared to the SOC group: (A) superior clinical improvement; (B) a greater decrease in the biological markers of viral attack by SARS-CoV-2 (PCR, viral load); (C) a greater decrease in inflammatory markers (e.g. CRP and lymphopenia); (D) a greater decrease in parenchymal involvement (chest CT) on the seventh day post-randomization; (E) to define the optimal dosage of CPZ and its tolerance; (F) to evaluate the biological parameters of response to treatment, in particular the involvement of inflammatory cytokines. Patient recruitment along with the main and secondary objectives are in line with WHO 2020 COVID-19 guidelines. ConclusionThis repositioning of CPZ as an anti-SARS-CoV-2 drug offers an alternative and rapid strategy to alleviate the virus propagation and the infection severity and lethality. This CPZ repositioning strategy also avoids numerous developmental and experimental steps and can save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easy to manage side effects. Indeed, CPZ is an FDA-approved drug with an excellent tolerance profile, prescribed for around 70 years in psychiatry but also in clinical routine in nausea and vomiting of pregnancy, in advanced cancer and also to treat headaches in various neurological conditions. The broad spectrum of CPZ treatment — including antipsychotic, anxiolytic, antiemetic, antiviral, immunomodulatory effects along with inhibition of clathrin-mediated endocytosis and modulation of blood-brain barrier — is in line with the historical French commercial name for CPZ, i.e. LARGACTIL, chosen as a reference to its “LARGe ACTion” properties. The discovery of those CPZ properties, as for many other molecules in psychiatry, is both the result of serendipity and careful clinical observations. Using this approach, the field of mental illness could provide innovative therapeutic approaches to fight SARS-CoV-2.

Chlorpromazine Electro‐oxidation at BDD Electrode Modified with nZVI Nanoparticles Impregnated NiAl LDH

AbstractNanocomposite of nanoscale zero‐valent iron (nZVI) and layered double hydroxide (LDH) was used as modifier for boron‐doped diamond electrode in determination of anti‐psychotic drug chlorpromazine (CPZ). nZVI nanoparticles were prepared by liquid phase reduction of ferric chloride with sodium borohydride on the surface of NiAl LDH matrix owing to the strong exchange and confinement efficiency of LDH. The structure, binding and surface properties of the nZVI@LDH nanocomposite were monitored using powder X‐ray diffractometry, FT‐IR spectroscopy, scanning and transmission microscopy and BET techniques. The electrochemical properties of the modified electrode were investigated by CV and EIS, performed in a phosphate buffer containing ferro/ferricyanide as redox probe. The modified electrode exhibited excellent electrochemical performance compared with unmodified electrode. As regard potential application of the nanocomposite surface to the CPZ detection, square‐wave voltammetric signals showed a good linear correlation over CPZ concentrations in a broad range from 0.1 to 8.0 μM with low detection limit of 0.005 μM. Nevertheless, these results suggest that the proposed nanocomposite modifier surface provides exceptional synergy and significant enhancement effect to the voltammetric response of CPZ and thus could be applied as highly efficient and stable platform of sensors in clinical analysis.

Electrochemical determination of Chlorpromazine using l-Cysteine modified carbon paste electrode

The l-Cysteine modified carbon paste electrode (Cys-CPE) has been employed for the electrochemical determination of Chlorpromazine (CPM). The anodic behaviour of CPM was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). The Cys-CPE showed enhanced electrochemical conductivity and ease of electron transfer towards the oxidation of CPM in the potential range of 0.2 V to 1.2 V in 0.1 M phosphate buffer solution (PBS). Electrochemical impedance study (EIS) showed the charge transfer resistance at CPE (241.4 Ω) and Cys-CPE (219.5 Ω). Under the optimum experimental conditions the anodic peak current increased linearly with concentration of CPM in the range of 1–35 µM (for DPV) and 0.8–3.4 µM (for SWV), respectively. The detection limit for DPV and SWV were respectively found to be 0.0119 µM and 2.436 nM. The proposed method was successfully employed for the determination of CPM present in pharmaceutical samples.

Functionalization of a carbon nanofiber with a tetrasulfonatophenyl ruthenium(II)porphine complex for real-time amperometric sensing of chlorpromazine.

A carbon nanofiber functionalized with ruthenium(II)-tetrasulfonato phenyl porphine (CNF/Ru-TSPP) is shown to be viable sensor for amperometric determination of the antipsychotic drug chlorpromazine (CPZ). The hollow platelet structured Ru-TSPP combines with the hollow cylindrical tube-like structure of the CNF via π stacking interaction. The morphological and electro conductive properties of the electrode were characterized by spectrophotometric techniques. The CNF/Ru-TSPP modified electrode displays a large surface-to-volume ratio, good electron transport and good electrocatalytic activity. The amperometric sensor, typically operated at a potential 0.63V (vs. Ag/AgCl) exhibits a linear response in the 0.6nM to 1.1mM CPZ concentration range, has a 0.2nM detection limit, and a remarkably good electrochemical sensitivity (2.405μAμM-1cm-2). The sensor is selective, repeatable and reproducible. It was successfully applied to the determination of CPZ in spiked serum samples. Graphical abstract Schematic presentation of carbon nanofiber/ tetrasulfonatophenyl Ruthenium(II)porphine (CNF/Ru-TSPP) nanocomposite synthesis and application for the electrochemical determination of chlorpromazine(CPZ).

Synthesis of La3+/Co3O4 Nanoflowers for Sensitive Detection of Chlorpromazine

In this study, a sensitive electrochemical sensor for chlorpromazine was established based on La3+/Co3O4 nanoflower. The La3+/Co3O4 nanoflower exhibited superior electrochemical activity towards the oxidation of chlorpromazine. Electrochemical oxidation of chlorpromazine on the modified electrode was an diffusion-controlled process. Electrochemical oxidation peak currents linearly increased with chlor-promazine concentrations in the range of 0.5 and 400.0 μM. The detection limit was calculated as 0.08 μM. The La3+/Co3O4/GCE allowed to determine the chlorpromazine in real samples. The results indicated that the electrochemical sensor prepared in this study could be a very promising alternative to current analytical methods used to determine chlorpromazine.

Determination of psychotropic drug chlorpromazine using screen printed carbon electrodes modified with novel MIP-MWCNTs nano-composite prepared by suspension polymerization method

In this research, the suspension polymerization method was used for synthesis of the nano-composite between Molecularly Imprinted Polymers (MIP) and Multiwall Carbon Nanotubes (MWCNT) for the first time. The chlorpromazine (CPZ) drug was applied as template molecule. The MIP-MWCNT nanocomposite and the non-imprinted polymer (NIP-MWCNT) were used for modification of screen printed carbon electrodes (SPCEs) which were designed and manufactured by hand. The modified SPCEs were used for CPZ determination via a three-step procedure includes: CPZ extraction from sample solution, electrode washing and electrochemical measurement. After ensuring the appropriate response of MIP based sensors to CPZ, the factors affecting the performance of sensor were examined and the calibration curve was constructed under optimized conditions. The peak current showed a linear relationship with CPZ concentration in the range of 7.50 × 10−10–2.50 × 10−7 M (R2 = 0.9956) and the detection limit was calculated 2.96 × 10−10 M. The relative standard deviations for investigation of sensor’s repeatability and reproducibility were obtained 3.76 and 4.13% (n = 5) respectively. Finally, in order to evaluate the sensor’s ability to determination of chlorpromazine in samples with complex matrices, it used for assay of CPZ in tablet and spiked human urine samples.

Chlorpromazine toxicity is associated with disruption of cell membrane integrity and initiation of a pro-inflammatory response in the HepaRG hepatic cell line

Chlorpromazine (CPZ) is a neuroleptic drug and prototype compound used to study intrahepatic cholestasis. The exact mechanisms of CPZ induced cholestasis remain unclear. Rat hepatocytes, or a sandwich culture of rat and human hepatocytes, have been the most commonly used models for studying CPZ toxicity in vitro. However, to better predict outcomes in pre-clinical trials where cholestasis may be an unwanted consequence, a human in vitro model, based on human HepaRG cells, capable of real-time, non-invasive and label free monitoring, alongside molecular investigations would be beneficial. To address this we used the human hepatic HepaRG cell line, and established concentrations of CPZ ranging from sub-toxic, 25 μM and 50 μM, to toxic 100 μM and compared them with untreated control. To assess the effect of this range of CPZ concentrations we employed electrical cell-substrate impedance sensing (ECIS) to measure viability and cell membrane interactions alongside traditional viability assays, immunocytostaining and qRT-PCR to assess genes of interest within adaptive and inflammatory pathways. Using these methods, we show a concentration dependant response to CPZ involving pro-inflammatory pathway, loss of tight junctions and membrane integrity, and an adaptive response mediated by Cytochrome P450 (CYP) enzyme activation and up-regulation of membrane phospholipid and xenobiotic transporters. In conclusion, structural changes within the membrane caused by sub-toxic and toxic concentrations of CPZ negatively impact the function of the cellular membrane. Damage to efflux transport proteins caused by CPZ induce cholestasis alongside downstream inflammation, which activates compensatory responses for cell survival. Lay summaryChlorpromazine is a drug used to treat patients with schizophrenia, which has a known association with liver damage. Here we show that it causes inflammation and alters the cell membranes in liver and bile duct cells similar to what is seen within a human population. The initiation of the inflammatory response and changes to cellular structure may provide insight into the damage and disease process and inform medical treatment.

Reversing Antimicrobial Resistance in Multidrug-Resistant Klebsiella pneumoniae of Clinical Origin Using 1-(1-Naphthylmethyl)-Piperazine.

Eleven clinical Klebsiella pneumoniae fluoroquinolone-resistant isolates were tested to access the potential of adjuvant therapies to reduce antimicrobial resistance using fixed concentrations of the chemosensitizers chlorpromazine (CPZ), thioridazine (TZ), phenylalanine-arginine-β-naphthylamide (PAβN), and 1-(1-naphthylmethyl)-piperazine-(NMP) with varying concentrations of antimicrobial agents nalidixic acid (NAL), ciprofloxacin (CIP), moxifloxacin (MXF), tetracycline (TET), and chloramphenicol (CHL). Ethidium bromide dye was used together with the chemosensitizers to investigate permeabilization effects. NMP was assessed for its capacity to reduce the mass of biofilm alone and in combination with CIP and MXF. Of the selected chemosensitizers, NMP exhibited the greatest capacity to reverse resistance and inhibit efflux, based on the concentrations tested. Susceptibility to antimicrobial agents including (fluoro)quinolones, TET, and CHL were found to be increased in the presence of NMP, in a concentration-dependent manner. PAβN also demonstrated similar effects when combined with the chemosensitizers tested. In the case of half of the isolates studied, NMP alone reduced preformed biofilm biomass. Combinations of latter along with CIP or MXF were also found to reduce the mass of preformed biofilm, in the case of only some of the bacterial isolates. The capacity of NMP to reduce antimicrobial resistance could be of relevance as a strategy to limit bacterial colonization on abiotic surfaces.