Search

Key Points: Question: Does the increase in risk of transition to psychosis associated with baseline antipsychotic dose in individuals at clinical high risk of psychosis (CHR-P) follow a dose-effect pattern? Findings: In this systematic review and meta-analysis of 290 individuals at CHR-P from 8 studies, those who were exposed to higher antipsychotic doses at baseline had an increased likelihood of transitioning to psychosis compared to those exposed to lower doses. Meaning: The findings suggest that evaluating baseline antipsychotic dosage could enhance current CHR-P criteria-based risk stratification and improve the precision of outcome prediction models, leading to a more personalized approach to treatment management. This systematic review and meta-analysis evaluates the association of baseline antipsychotic dose and transition to psychosis among individuals at high risk for psychosis. Importance: Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics is associated with an increased risk of transitioning to psychosis in individuals at clinical high-risk for psychosis (CHR-P) and that such effect is not a result of pretest risk enrichment. However, to maximize its translational utility for prognostic stratification in clinical practice, testing for the potential presence of a dose-response association is crucial. Objective: To test whether the negative prognostic effect of baseline antipsychotic exposure in individuals at CHR-P follows a dose-effect pattern, as indicated by mean chlorpromazine equivalent doses (CPZ-ED). Data Sources: MEDLINE and Cochrane Library, performed up to August 31, 2023, searching for English-language studies on individuals at CHR-P reporting data on exposure to antipsychotics at baseline and detailed information on dosage by transition status. Study Selection: Studies that provided information on antipsychotic exposure at baseline and included detailed dosage data categorized by transition status. Data Extraction and Synthesis: Eligible studies were identified following PRISMA guidelines and evaluated independently by 2 reviewers with the Newcastle-Ottawa Scale for assessing the quality of nonrandomized studies in meta-analyses. Main Outcomes and Measures: The primary outcome was transition to psychosis in individuals at CHR-P who were receiving antipsychotic treatment at baseline, measured by baseline mean CPZ-ED in individuals at CHR-P who transitioned to psychosis compared to those who did not. Results: Eight studies were included in the systematic review and meta-analysis. Among 290 individuals at CHR-P (mean [SD] age, 19.4 [2.6] years) who were exposed to antipsychotics at baseline and remained in contact up to the completion of the study, 66 converted to psychosis and 224 did not. The mean CPZ-ED ranged 60 to 395 mg/d in those who converted and 13 to 224 mg/d in those who did not. Those who converted to psychosis had higher CPZ-ED than those who did not in both the common-effects model (Hedges g, 0.41; 95% CI, 0.12-0.70; z, 2.78; P =.005) and in the random-effects model (Hedges g, 0.41; 95% CI, 0.15-0.67; z, 3.69; P =.008; τ2, 0.0). There was no relevant heterogeneity (Cochran Q, 3.99; df, 7; P =.78; I2, 0.0%; 95% CI, 0.0-68.0). The radial plot indicated a good fit of the model. Conclusions and Relevance: In individuals at CHR-P who were exposed to antipsychotics at baseline, those receiving higher antipsychotic doses demonstrated an increased likelihood of transitioning to psychosis. This meta-analytic evidence of putative dose-effect association confirms that baseline antipsychotic exposure and the corresponding dosage carry salient prognostic information that could improve current CHR-P criteria-based risk stratification at inception. [ABSTRACT FROM AUTHOR]

Background: Acupuncture is a non-pharmacological therapy used clinically for mood disorders. Relief of physical symptoms with acupuncture treatment may lead to relief of depressive symptoms and improvement of quality of life (QoL). Few studies have examined the effect of acupuncture on the physical symptoms and QoL of patients with mood disorders. Objectives: To examine the effect of acupuncture on physical symptoms and QoL of patients with treatment-resistant major depressive disorder (MDD) and bipolar disorder (BD). Methods: This prospective, single-arm, longitudinal study included patients with MDD and BD from an outpatient psychiatric clinic. Acupuncture was performed weekly for 12 weeks in combination with regular treatment, with fixed acupoints and individualized treatment for each patient. Psychiatric symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS). Physical symptoms such as physical pain, gastrointestinal symptoms, and sleep disorders were evaluated using the Japanese version of the Somatic Symptom Scale-8 (SSS-8) and Visual Analog Scale (VAS). QoL was evaluated using the 8-item Short-Form (SF-8) Health Survey. Results: A total of 36 patients (15 MDD and 21 BD patients) were analyzed. After 12 weeks of acupuncture, HSDS and HSAS scores significantly decreased (p < 0.05). Physical symptoms evaluated using SSS-8 and VAS scores also significantly improved (p < 0.05). In particular, neck pain and insomnia improved at an early stage. Among the SF-8 subscales, scores of bodily pain, general health perception, role limitations due to emotional problems, and mental health significantly increased (p < 0.05). Conclusion: Acupuncture may improve not only psychiatric symptoms but also physical symptoms and QoL in patients with treatment-resistant mood disorders. Further studies are required for confirmation of the preliminary data collected thus far. [ABSTRACT FROM AUTHOR]

Objectives: Stroke is an important cause of death and disability. Recent evidence suggests that post-stroke inflammation is an important factor in stroke pathology and a root cause of its lasting consequences. Phenothiazine drugs, like chlorpromazine and promethazine (C + P), induce hypothermia and have been shown to play a major role in neuroprotection. In the present study, we investigated this neuroprotective mechanism by assessing the anti-inflammatory effect of these drugs. Methods: Adult Sprague-Dawley rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 6 or 24 h of reperfusion, with or without C + P (8 mg/kg). Infarct volumes, neurological deficits, along with mRNA and protein quantities of receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), NLRPyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β) were assessed, as well as the infiltration of neutrophils and macrophages. Results: C + P induced hypothermia that significantly reduced RIP1, RIP3, NLRP3 and IL-1β expression, infarction, and immune cell infiltration, while C + P treatment with temperature control at 37°C induced lesser effect. Conclusion: These findings suggest that the anti-inflammatory effect of C + P may be dependent on drug-induced hypothermia and regulation of the NLRP3 inflammasome via the RIP1/RIP3 complex. Future investigations are needed regarding C + P as potential treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

The primary objective of the study was to investigate the mucoadhesion and gelling behaviour of mucilage isolated from the tubers of Eulophia herbacea (Orchidaceae), and to search the possibility of enhanced brain targetability through naso-brain delivery of stearylamine-tailored cationic neuronanoemulsions (cNNEs)-laden hydrogel formulation. The NNEs were fabricated using hot high-pressure homogenisation technique and optimised using Box-Behnken experimental design. The optimised sample of NNEs was surface-tailored with stearylamine to prepare cNNEs that were further loaded into mucilage-based mucoadhesive hydrogel formulation. The isolated tuber mucilage was found to contain the carbohydrates. The globule size and ζ-potential of CPZ-loaded NNEs were observed in a range of 27.49 ± 2.4 to 284.4 ± 6.2 nm, and −10.3 ± 1.2 to −15.4 ± 1.0 mV, respectively. For cNNEs, globule size, and ζ-potential were 32.42 ± 2.8 nm and 28.21 ± 0.4 mV, respectively. The bioadhesion potential of hydrogel was observed to be 18,622 mN, indicating its highly bioadhesive nature. Extensive characterisation at preclinical level appraised that it is a promising drug delivery approach. [ABSTRACT FROM AUTHOR]

Natural clay minerals and their nanocomposites are being increasingly studied for environmental remediation applications because of their abundance and unique surface properties. Halloysite nanotubes (HNTs) were modified with carbon spheres derived from guar gum through hydrothermal treatment, resulting in CS@HNTs. ZnO nanorods (ZnO-NRs) were synthesized via a sol-gel process and then loaded onto CS@HNTs, which enhanced their photocatalytic and electrochemical activities by widening their band structure and light absorption capabilities. The physicochemical and optoelectronic properties of the resulting CS@HNTs/ZnO-NRs nanocomposite was confirmed. The electrochemical detection of CPZ in the presence of CS@HNTs/ZnO/SPCE nanocomposite resulted in an excellent detection limit (LOD = 0.01 µM), sensitivity (1.917 µAµM–1 cm–2), and a wide linear range of detection (0.08–83.56 µM). Photocatalytic experiments were performed using the antibiotics tetracycline hydrochloride (TC) and CPZ under simulated solar irradiation. The degradation efficiency was 85.34 % and 83.84 %, respectively, due to the rapid charge carrier transport and reduced recombination. These findings demonstrate the excellent photocatalytic and electrocatalytic performance of the synthesized CS@HNTs/ZnO-NRs bifunctional catalyst. [Display omitted] • CS@HNTs/ZnO-NRs photo(electro)catalyst was synthesized by a two-step process. • Carbon modification on HNTs achieved using guar gum biopolymer material. • CS@HNTs/ZnO-NRs/SPCE sensor results in excellent detection limit and sensitivity. • CS@HNTs/ZnO-NRs exhibit 85.34 % of TC photodegradation (k = 0.011 min–1). • S-scheme charge transfer enables efficient charge separation and high efficiency. [ABSTRACT FROM AUTHOR]

In this work, tungsten disulfide (WS2) nanosheets were obtained from bulk WS2 by electrochemical exfoliation and employed for the development of novel, sensitive and selective sensor for the determination of chlorpromazine (CPZ). It is worth mentioning that for the first time a glassy carbon (GC) electrode modified with WS2 sheets is employed for the quantitative voltammetric determination of CPZ in human urine samples. A pair of well-defined reversible CPZ redox peaks (560 and 500 mV) is observed at WS2 modified GC electrode due to the high surface area and excellent electrocatalytic activity of WS2 sheets towards CPZ oxidation and reduction reaction. The GC/WS2 sheets modified electrode exhibited a low detection limit of 4 µMtowards CPZ. Further, the sensitivity of the GC/WS2 sheets modified electrode is found to be 1.416 µA cm-2 mM-1 over a linear range of 0-0.69 mM. Finally, the application of as-fabricated electrode for determination of CPZ in human urine samples is demonstrated. [ABSTRACT FROM AUTHOR]

Abstract The residues of pharmaceutical and personal care products are the cause of increasing concern around the world. The aim of this study was to carry out the quantification of six antipsychotic drugs in hospital wastewater with the aid of liquid chromatography-mass spectrometry and, subsequently, make a preliminary assessment of the environmental risk posed. Dispersive liquid-liquid microextraction and solid phase extraction were optimized by multivariate design and validated in compliance with international guidelines. The extraction procedures were successfully applied to the quantification of the six selected antipsychotics in samples that were formed each day and collected at two main sampling points of the sewage network over the period of a week, in December 2017. Olanzapine (0.31─0.52 µg L-1), clozapine (0.56─0.97 µg L-1), haloperidol (1.43─2.73 µg L-1), risperidone (0.92─0.98 µg L-1) and chlorpromazine (0.52 µg L-1) were found in at least one sampling point. In the case of most analytes, the highest concentrations were determined at sampling point A, which are derived from the psychiatric wing. The environmental risk quotient for clozapine, chlorpromazine and risperidone was ˃600, a very high-risk index, which signals the need for a better control of the emission of antipsychotics and an improvement of the wastewater treatment, especially, with regard to wastewater discharged from the hospital psychiatric wing. Graphical abstract fx1 Highlights • DLLME and SPE procedures were multivariate optimized and validated. • Five of the six antipsychotics were sequentially determined in hospital wastewater. • Clozapine, chlorpromazine and risperidone showed a high potential ecological risk. • There is a greater concern about antipsychotics in hospital wastewater. [ABSTRACT FROM AUTHOR]

Highlights • We propose the first time PNIPAM microgel modified GCE for the detection of antipsychotic drug chlorpromazine (CPZ). • The linear response range of the CPZ sensing platform is from 0.05 to 7999 µM. • LOD and sensitivity is found to be 0.016 µM and 0.084 µAµM−1cm−2, respectively. • The PNIPAM microgel modified GCE showed an excellent selectivity even in the existence of co-interfering electroactive species. • We successfully applied to the real samples analysis in human urine and serum with satisfactory results. Abstract Nowadays, smart polymers have been received a great attention in biomedical applications, especially in sensors because of their novel and peculiar properties. In this study, sphere-like structure of poly-N-isopropylacrylamide (PNIPAM) microgel was prepared via one-step precipitation polymerization method. Cyclic voltammetry and electrochemical impedance spectroscopy experiment showed that the PNIPAM microgel could enhance the electrochemical performance of the electrodes, as a consequence of the large surface area presented by the PNIPAM. The PNIPAM microgel modified glassy carbon electrode (PNIPAM microgel modified GCE) exhibited an enhanced electrocatalytic activity towards antipsychotic drug chlorpromazine (CPZ) detection. The electrochemical response of CPZ using PNIPAM microgel modified GCE was linear over the range from 0.05 to 7999 µM. The sensitivity and limit of detection were 0.084 µAµM−1cm−2 and 0.016 µM, respectively. In addition, the sensor is highly sensitive, selective and durable even in the presence of potentially interfering electroactive compounds. The good analytical performance of the PNIPAM microgel modified GCE was confirmed for determining trace level CPZ in human serum and urine samples with satisfactory results. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Highlights • We have developed ytterbium tungstate (Yb 2 WO 6) as an electrocatalyst through a simple co-precipitation method. • The as-prepared catalyst was investigated by various characterization. • The as-developed Yb 2 WO 6 was successfully applied to the electrochemical sensor (electrocatalyst) for detection of antipsychotic drug chlorpromazine (CPZ). • The proposed (Yb 2 WO 6 /SPCE) shows an excellent electrocatalytic activity towards CPZ with extented wide linear response range (0.01-2520 μM) and lower detection limit (0.001 μM). • The Yb 2 WO 6 /SPCE displays an appreciable stability, and repeatability towards CPZ sensing. In addition, the Yb 2 WO 6 /SPCE was successfully applied to real sample analysis in CPZ tablet and urine samples with acceptable recoveries. Abstract In this work, we have developed ytterbium tungstate (Yb 2 WO 6) as an electrocatalyst through a simple co-precipitation method. The as-prepared catalyst was systematically investigated by various characterization techniques such as X-ray diffraction (XRD), Raman spectroscopy, field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray analysis (EDX). The as-developed Yb 2 WO 6 was successfully applied to the electrochemical sensor (electrocatalyst) for sensitive and selective detection of antipsychotic drug chlorpromazine (CPZ). Interestingly, the Yb 2 WO 6 modified screen printed carbon electrode (Yb 2 WO 6 /SPCE) shows an excellent electrocatalytic activity towards CPZ with extented wide linear response range and lower detection limit of 0.01–2520 µM and 0.001 µM, respectively. Moreover, the as-developed Yb 2 WO 6 /SPCE delivered an excellent selectivity even in the existence of cation, anion and some biologically co-interfering compounds. Furthermore, the Yb 2 WO 6 /SPCE displays an appreciable stability, and repeatability towards CPZ sensing. In addition, the Yb 2 WO 6 /SPCE was successfully applied to real sample analysis in CPZ tablet and urine samples with acceptable recoveries. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Highlights • A rice bundle like nickel phosphate was successfully synthesized by simple hydrothermal method. • An electrochemical sensor was proposed for the detection of chlorpromazine using rice bundle like nickel phosphate. • A very low detection limit, excellent sensitivity and rapid response could be achieved by this proposed sensor. Abstract The exploration of highly active and cost-effective catalysts for the electrochemical sensor is crucial to facilitate the improvement in detection techniques. In this study, we report a facile hydrothermal synthesis of nanostructured nickel phosphate (NiP) for the application towards the electrochemical determination of chlorpromazine (CPZ) in biological samples. The synthesized nanostructured NiP was characterized using powder X-ray diffraction, Fourier transforms infrared spectroscopy, field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy and elemental mapping techniques. The characterization results exhibit that the prepared electrocatalyst material showed rice bundle-like nanostructure. Furthermore, electrochemical impedance spectroscopy, cyclic voltammetry and differential pulse voltammetric techniques were performed to analyze the electrochemical properties of the prepared nanocomposite. Remarkably, as-prepared rice bundle like NiP modified electrode delivers an excellent sensing performance for the detection of CPZ. The nanostructured NiP modified electrode showed the excellent linear range (0.008–34 µM; 36–221.4 µM), low-level detection limit (0.002 µM) and high sensitivity (8.526 µA/µM cm2), which is superior to that of all other electrocatalysts to sense CPZ. The most active nanostructured NiP modified electrode exhibited good selectivity towards CPZ, and the detection of CPZ in real sample (human urine) showed satisfactory recoveries. Thus, this facile and super active nanostructured NiP material proven to be a promising electrode material in electrochemical sensors. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

The maximum allowed limits of chlorpromazine (CPZ) established by Food and Drug Administration (FDA) for children aged between 1 and 5 years is 0.125 mM and between 6 to 12 years is 0.235 mM. However, excess consumption of CPZ beyond these permissible limit cause adverse health effects. In order to detect CPZ, herein, we employ NiFe-layered double hydroxide sheets modified glassy carbon electrode (GC/NiFe LDH). The GC/NiFe LDH electrode exhibited a good electrocatalytic activity towards CPZ detection at a less working potential even in the presence of interferents such as ascorbic acid, uric acid, glucose, sucrose, fructose and acetaminophen. The anodic peak observed at 614 mV (vs. Ag/AgCl) corresponds to the oxidation of CPZ and the proposed platform exhibited an excellent linearity in the range 75 μM to 1.0 mM. Further, the GC/NiFe LDH electrode exhibited an excellent sensitivity (1.05 μA μM-1 ), repeatability (0.86% RSD), reproducibility (1.54% RSD) and limit of detection (1.23 μM). [ABSTRACT FROM AUTHOR]

Parkinsonism is characterized by rest tremor, inflexibility, balance debilitation, slow motion and dementia. It is known to be caused by the deficiency of dopaminergic neurons in nigrostriatal pathway. Different studies propose that oxidative burden may be included in the apoptotic process in parkisnons disease. Zamzam water being alkaline in composition may diminish the oxidative stress and hence relieve the symptoms. Therefore, the purpose of this study was to explore the neuroprotective effect of zamzam water in chlorpromazine induced animal model of Parkinsonism. Results revealed that zamzam water did not show significant anticataleptic effect after 21 days as compared to chlorpromazine treated group. However, after 30 days of giving zamzam water showed highly significant decrease (p<0.001) in cataleptic score as compared to chlorpromazine treated group that is negative control. After 30 days of dosing, cataleptic scores by zamzam water were closer to standard drug but standard drug (levodopa/carbidopa) still showed better results than zamzam water. Results from histopathological study of rat's brain also revealed regenerative changes by zamzam treated water when compared with negative control. This regenerative change after zamzam water treatment might play a positive role in future if administered continuously. These results also suggest that zamzam water can be used in combination with standard drug to produce synergistic effect in the management of parkinsons disease. [ABSTRACT FROM AUTHOR]

In this study, a new modified electrode was proposed to measure chlorpromazine hydrochloride (CPH). Carbon paste electrode was modified with vanadium pentoxide (V 2 O 5 ) and titanium dioxide (TiO 2 ) nanoparticles and graphene (TVGCPE). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods were used to analyze the prepared electrode. The catalytic property resulting from the synergistic effect of these three modifiers not only increased the oxidation current but also reduced the oxidation potential of CPH. Scan rate and pH effects on the performance of TVGCPE electrode were also investigated. The linear calibration curve of CPH was obtained within the linear range of 3.30 × 10 −8 –8.5 × 10 −4  M, and the detection limit was calculated as 5.3 × 10 −9  M. Finally, the modified electrode was successfully used to measure CPH in some real samples such as blood serum and pharmaceutical samples. [ABSTRACT FROM AUTHOR]

Pharmaceutical waste products have become environmental contamination and pollution which poses a significant risk to our planet. The fabrication of effective antipsychotic drug monitoring systems is greatly important to minimize their environmental problems. Therefore, the construction of mixed metal molybdates has been investigated to develop an electrochemical sensor with high sensitivity and low detection limits. In regards, we have successively synthesized nickel molybdate/cobalt molybdate (NiMoO 4 /CoMoO 4 ; NCMO) through a simple co-precipitation method and their electrocatalytic activity of chlorpromazine (CPZ) evaluated. The synthesized NCMO was inspected by diverse physicochemical analyses. From the morphological study, the prepared NCMO nanoflake displays exceptionally rich surface electroactive sites. Furthermore, the electrochemical properties of the developed sensor were investigated through cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). Accordingly, the NCMO endorses greater electrochemical behavior because of rapid electron transfer, improved electrochemical active surface area, and synergetic effect. The established electrochemical sensor displays a wide linear range and the lowest detection limit, admirable sensitivity, reproducibility, and repeatability. Finally, the real-time application of CPZ was performed in wastewater and human urine samples with reasonable recoveries. [Display omitted] • We propose mixed metal molybdate (NiMoO 4 /CoMoO 4) via a simple co-precipitation method. • NCMO is demonstrated to be a sensitive and selective electrochemical detection of the antipsychotic drug chlorpromazine. • NCMO modified screen-printed carbon electrode has detected wide linear range and nanomolar level. • Real sample analyses validate the practical feasibility of the developed sensor with satisfactory results. [ABSTRACT FROM AUTHOR]

Background: Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. Methods: The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphineinduced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. Results: The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin's test. No lethality was observed after 24 h posttreatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphineinduced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. Conclusions: The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effects of using ciproxifan (CPX) and clobenprofit (CBP) on MK-801-induced schizophrenia behaviors in mice with topics including N-methyl-d-aspartate receptor blockade, ketamine induction as well as horizontal locomotor activity evaluation.

Objective To investigate the gene related to β-lactam resistance and to confirm the mechanism about a synergy effect between CPZ and β-lactam antibiotics. Methods To measure antibacterial activity, we performed a minimum inhibitory concentration (MIC) and synergy test. Transmission electron microscopy (TEM) was used in morphological analysis. To analyze gene expression, we conducted reverse transcriptase polymerase chain reaction (PCR). Results We confirmed a synergy effect between CPZ and β-lactam antibiotics. Furthermore, we observed that CPZ affect the cell envelope of MRSA by using TEM. At the gene level, CPZ reduced the expression of resistance genes. Conclusions Through this result, we hypothesize that a decrease of resistance factor expressions was caused by CPZ because it disrupts the activity of a sensor protein located in the cell membrane. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning. [ABSTRACT FROM AUTHOR]

The increasing occurrence of pharmaceutical drugs in the aquatic environment is cause of concern, due to the possibility of toxic phenomena in non-target species, including oxidative stress and neurotoxicity. The present study aimed to assess the acute effect of four widely used therapeutic agents: acetaminophen (analgesic), chlorpromazine (antipsychotic), diclofenac (anti-inflammatory) and propranolol (antihypertensive), in the cladoceran species Daphnia magna. Considering the involvement of the mentioned compounds in the impairment of cholinesterasic activity and modifications in cellular redox systems, the purpose of this study was to analyze their effects on biomarkers of neuronal regulation, such as total cholinesterases (ChEs), and enzymatic oxidative stress defense, including as catalase (CAT), glutathione-S-transferases (GSTs), and total and selenium-dependent glutathione-peroxidase (total GPx; Se-GPx) activities. Exposure to acetaminophen caused a significant inhibition of AChE and Se-GPx activities in D. magna relative to the control. Among the biomarkers of oxidative stress, only the activity of CAT was significantly altered in concentration of 0.001 mg L −1 of chlorpromazine, which was not always consistent with the literature. Diclofenac caused a significant inhibition of AChE and Se-dependent GPx, and also in total GPx activities. Propranolol was responsible for a significant decrease in the activity of the latter two enzymes, and also a slight increase of GSTs activity. The results indicated that the exposure to all the tested compounds induced alterations on the cellular redox status in the studied species. In addition, acetaminophen and diclofenac were shown to have the capability of interfering with D. magna neurotransmission, through the inhibition of ChEs. Our data enlighten the need for more research on the ecological consequences of pharmaceuticals in non-target organisms. [ABSTRACT FROM AUTHOR]

The effects of chlorpromazine-treatment timing on the development of the placenta in pregnant rats were examined. Chlorpromazine was administered intraperitoneally at 100 mg/kg on gestation day (GD) 11 (GD11-treated group), GD 13 (GD13-treated group) or GD 15 (GD15-treated group) into pregnant rats. All treated dams exhibited decreased body weight, prone position, hypothermia, loss or decrease of locomotor activity, etc. The fetal mortality rates were increased up to 42.9% in the GD11- and GD13-treated groups and up to 16.7% in the GD15-treated group. The embryo/fetal weight was on a declining trend from GD 16 onward, and the intrauterine growth retardation (IUGR) rates on GD 21 were increased in all treated groups. The placental weight showed a declining trend from GD 15 onward in all treated groups. Histopathologically, apoptosis was detected 1 or 2 days after treatment, and led to hypoplasia in the labyrinth zone and metrial gland, and cystic degeneration in the basal zone on GD 21 in all treated groups. There was no difference in the histopathological lesions on GD 21 among the treated groups. Thus, it is considered that chlorpromazine-induced placental toxicity is characterized in that there is no obvious specific sensitive period from GD 11 to GD 15. Chlorpromazine induced a non-specific transient development retardation of the placenta by apoptosis independently of the cell proliferation period in each part/zone. [ABSTRACT FROM AUTHOR]

Objective To analyse the efficacy of diethylcarbamazine (DEC), tetramisole and chlorpromazine on the longevity and activity of glucose-6-phosphatase and succinate dehydrogenase in the microfilariae recovered from the peripheral circulation of the rats before and after the treatment. Methods Setaria cervi worms were implanted in white rats via laparotomy and microfilaraemic rats were divided into 4 groups. Groups 1, 2 and 3 were treated with DEC, tetramisole and chlorpromazine respectively, while Group 4 served as infected control. Longevity of microfilariae and differential leucocyte counts were recorded till the disappearance of microfilariae from peripheral blood. Glucose-6-phosphatase and succinate dehydrogenase enzymes were localized in the microfilariae recovered from normal and treated rats. Results The microfilariae survived for 48 days in untreated rats while survival was reduced to 15, 21 and 27 days after treatment with DEC, tetramisole and chlorpromazine, respectively. Eosinophils and neutrophils increased during 2nd and 3rd weeks, whereas the lymphocytes increased during 4–7 weeks. DEC treatment resulted in slight decrease in the localization of succinate dehydrogenase but not in glucose-6-phosphatase. Tetramisole and chlorpromazine treatment did not show any appreciable change in the localization of both the above enzymes. Conclusions DEC proved the most effective drug which cleared the microfilaraemia within 15 days and reduced the activity of succinate dehydrogenase to some extent followed by tetramisole and chlorpromazine which took more time for the clearance of microfilariae and had no effect on the localization of both glucose-6-phosphatase and succinate dehydrogenase. [ABSTRACT FROM AUTHOR]

Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors – neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R) – both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling – a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic pathways, which has potential clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: Hypothermia is a well-recognised and effective neuroprotectant because of its depressive effect on metabolism. However, its application in focal ischaemic stroke is limited by delayed onset, prolonged duration, the need for extensive medical and nursing efforts and significant complications. This study combined mild hypothermia with phenothiazine drugs to enhance its neuroprotective effects, thus potentially avoiding side effects. Methods: Fifty-four male Sprague-Dawley rats were induced with a 2-hour right middle cerebral artery (MCA) occlusion using an intraluminal filament. Five groups were tested: the stroke group without treatment (anal temperature 37.8-38.3°C), the mild hypothermia group (anal temperature 35.0°C), the drugs group (1 mg/kg chlorpromazine and 1 mg/kg promethazine, anal temperature at 37.8-38.3°C), combination therapy with the mild hypothermia and drugs group and the normal control group (anal temperature 37.8-38.3°C). The treatments immediately followed reperfusion. The extent of brain injury was evaluated by infarct volume and behaviour performance. Results: The combination treatment of mild hypothermia with phenothiazine drugs demonstrated salient and significant (P<0.001) reductions in infarct volume (30.0± 15.14%) when compared to the stroke group (52.77 ± 8.99%). A better recovery of long-term motor performance was also observed for those receiving the combination therapy. However, when administered independently, neither the mild hypothermia therapy (53.8±10.3%) nor phenothiazine regimen (55.7±9.00%) had significant therapeutic effects on infarct volume (P= 0.85 and 0.61, respectively). Discussion: This study provides a novel and promising therapeutic strategy in the management of acute stroke. [ABSTRACT FROM AUTHOR]

Chlorpromazine is psychotropic drug, which molecule consisting of three condensed aromatic rings enables intercalation into DNA double helix. In our research we focused on designing biosensor which allows to detect chlorpromazine or other phenotiazines selectively, in samples of complex matrices. The experiments were carried out with DNA-modified gold amperometric sensors, fabricated by direct writing, by means of microdosing robot. The electrochemical detection of chlorpromazine in range 5 μM – 50 μM after 2-minute incubation was performed by linear sweep voltammetry (LSV) at room temperature. Using the developed DNA-modified gold paste electrodes, micromolar concentrations of chlorpromazine in analyzed samples can be detected. In comparison of chlorpromazine detection on bare gold and DNA-modified electrodes, increase of oxidation peak current was observed. Low limit of detection (LOD) of the developed amperometric sensors for chlorpromazine was determined at the level below 0.6 μM. In samples containing electrochemically active interfering substances only oxidation peak for chlorpromazine was present. [ABSTRACT FROM AUTHOR]

Copyright of Revista Colombiana de Gastroenterología is the property of Asociacion Colombiana de Gastroenterologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chlorpromazine is a low potency “typical” antipsychotic agent used to treat schizophrenia. It continues to be prescribed frequently in India owing to its lower cost. There have been previous reports of ocular adverse effects with prolonged use of chlorpromazine. We report three patients who developed corneal and lenticular opacities secondary to prolonged chlorpromazine use leading to visual impairment. Early detection of ocular deposits and switching over to risperidone from chlorpromazine helped in the reversal of chlorpromazine- induced ocular side effects in one of them. The case series further adds evidence to the causative relationship between chlorpromazine and ocular side effects. [ABSTRACT FROM AUTHOR]

A simple, rapid and sensitive method termed as magnetic solid phase extraction (MSPE) combined with high-performance liquid chromatography-ultraviolet detector (HPLC-UV) has been proposed for the determination of trace amounts of chlorpromazine (CPZ) in water, urine and plasma samples. The separation and determination was performed on a C18 column under the optimal chromatographic conditions. Several factors influencing the extraction efficiency of CPZ, such as pH, surfactant and adsorbent amounts, ionic strength, extraction time, sample volume and desorption conditions, were studied and optimized. Under the optimal MSPE conditions, the extraction percentage of CPZ was 74%, 27% and 16% in water, urine and plasma samples, respectively. The limits of detection (LODs) of the proposed approach were 0.1, 5.0 and 10 ng/mL in water, urine and plasma samples, respectively. The relative standard deviations (RSDs) based on five replicate determinations at 10 ng/mL level of CPZ was 1.2%. Good linear behaviors over the investigated concentration ranges (0.25-300 ng/mL) with good coefficient of determination, R²>0.9998, were obtained. Good spike recoveries with relative errors less than 9.0% were obtained when applying the proposed method to water, urine and plasma samples. [ABSTRACT FROM AUTHOR]

Abstract: We examined the sequential histopathological changes in the placentas from rats exposed to chlorpromazine. Chlorpromazine was intraperitoneally administered on GD 14 at 50 and 100mg/kg and the placentas were sampled on GDs 14.5, 15, 17 and 21. The incidence of dams with complete fetal resorption was increased from GD 17 up to 20% at 50mg/kg and 44.4% at 100mg/kg. The embryo/fetal weights reduced on GDs 15 and 17 at 50mg/kg and during GDs 15–21 at 100mg/kg. The placental weights reduced on GD 17 at 50mg/kg and during GDs 14.5–21 at 100mg/kg. Histopathologically, in the labyrinth zone, apoptotic cells were scattered in the trophoblastic septa without inhibition of cell proliferation on GDs 14.5 and 15 at 50 and 100mg/kg in a dose-dependent manner. A decrease in trophoblasts led to labyrinth zone hypoplasia. In the basal zone, apoptotic cells were scattered on GDs 14.5 and 15 at 100mg/kg, and most of them appeared to be glycogen cells. A decrease in glycogen cells induced the delayed development of glycogen cell islands and the subsequent remaining glycogen cell islands, and led to the cystic degeneration of glycogen cells. In addition, failure of development of the glycogen cell islands led to the impaired interstitial invasion of the glycogen cells, and then metrial gland hypoplasia occurred. [Copyright &y& Elsevier]

Background/purpose: The purpose of the study was to investigate relationship between saliva flow rates, estrogen levels, and caries prevalence in female psychiatric patients under antipsychotic therapy. Materials and methods: Sixty-one institutionalized psychiatric females (31 patients treated with chlorpromazine only and 30 patients treated with chlorpromazine and biperiden) were compared with 36 unmedicated healthy females. The unstimulated whole saliva (UWS) flow rate and serum estrogen were measured. Caries prevalence was recorded in terms of decayed, missing, and filled teeth (DMFT). Results: The UWS flow rate in the control group was 0.35+ 0.18 mL/min and the DMFT 18.8+ 5.7. In comparison, UWS flow rates were 0.25 + 0.15 mL/min (P = 0.003) and 0.07 + 0.05 mL/min (P= 0.000) in patients on chlorpromazine and patients on chlorpromazine as well as biperiden, respectively, and DMFT values were 22.7 + 4.6 (P = 0.003) and 26.5 + 5.3 (P = 0.000), respectively. Patientson chlorpromazine with amenorrhea had reduced UWS flowrate and estrogen levels with respect to controls (P=0.036; P=0.000, respectively). Correlation analysis revealed significant correlations between UWS flow rate and DT, DMFT, number of used drugs and estrogen level. Conclusion: It seems that chlorpromazine-induced hyposalivation included (apart from its antimuscarinic effect) a neuroendocrine effect which affected the estrogen levels. [ABSTRACT FROM AUTHOR]

Abstract: Studies of polystyrene nanoparticle (PNP) trafficking across mouse alveolar epithelial cell monolayers (MAECM) show apical-to-basolateral flux of 20 and 120nm amidine-modified PNP is ~65 times faster than that of 20 and 100nm carboxylate-modified PNP, respectively. Calcium chelation with EGTA has little effect on amidine-modified PNP flux, but increases carboxylate-modified PNP flux ~50-fold. PNP flux is unaffected by methyl-β-cyclodextrin, while ~70% decrease in amidine- (but not carboxylate-) modified PNP flux occurs across chlorpromazine- or dynasore-treated MAECM. Confocal microscopy reveals intracellular amidine- and carboxylate-modified PNP and association of amidine- (but not carboxylate-) modified PNP with clathrin heavy chain. These data indicate (1) amidine-modified PNP translocate across MAECM primarily via clathrin-mediated endocytosis and (2) physicochemical properties (e.g., surface charge) determine PNP interactions with mouse alveolar epithelium. Uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and (based on comparison with our prior results) specific epithelial cell type. From the Clinical Editor: In this study of polystyrene nanoparticle trafficking across mouse alveolar epithelial cell monolayers, the authors determined that uptake/trafficking of nanoparticles into/across epithelial barriers is dependent on both nanoparticle physicochemical properties and the specific type of epithelial cells. [Copyright &y& Elsevier]