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Food and Chemical Toxicology : An... Nov 2023Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and...
BACKGROUND
Emesis is a complex physiological phenomenon that serves as a defense against numerous toxins, stressful situations, adverse medication responses, chemotherapy, and movement. Nevertheless, preventing emesis during chemotherapy or other situations is a significant issue for researchers. Hence, the majority view contends that successfully combining therapy is the best course of action. In-vivo analysis offers a more comprehensive grasp of how compounds behave within a complex biological environment, whereas in-silico evaluation refers to the use of computational models to forecast biological interactions.
OBJECTIVES
The objectives of the present study were to evaluate the effects of Sclareol (SCL) on copper sulphate-induced emetic chicks and to investigate the combined effects of these compounds using a conventional co-treatment approach and in-silico study.
METHODS
SCL (5, 10, and 15 mg/kg) administered orally with or without pre-treatment with anti-emetic drugs (Ondansetron (ODN): 24 mg/kg, Domperidone (DOM): 80 mg/kg, Hyoscine butylbromide (HYS): 100 mg/kg, and Promethazine hydrochloride (PRO): 100 mg/kg) to illustrate the effects and the potential involvement with 5HT, D, M/ACh, H, or NK receptors by SCL. Furthermore, an in-silico analysis was conducted to forecast the role of these receptors in the emetic process.
RESULTS
The results suggest that SCL exerted a dose-dependent anti-emetic effect on the chicks. Pretreatment with SCL-10 significantly minimized the number of retches and lengthened the emesis tendency of the experimental animals. SCL-10 significantly increased the anti-emetic effects of ODN and DOM. However, compared to the ODN-treated group, (SCL-10 + ODN) group considerably (p < 0.0001) extended the latency duration (109.40 ± 1.03 s) and significantly (p < 0.01) decreased the number of retches (20.00 ± 0.70), indicating an anti-emetic effect on the test animals. In in-silico analysis, SCL exhibited promising binding affinities with suggesting receptors.
CONCLUSION
SCL-10 exerted an inhibitory-like effect on emetic chicks, probably through the interaction of the 5HT and D receptors. Further studies are highly appreciated to validate this study and determine the precise mechanism(s) behind the anti-emetic effects of SCL. We expect that SCL-10 may be utilized as an antiemetic treatment in a single dosage form or that it may function as a synergist with other traditional medicines.
Topics: Animals; Antiemetics; Serotonin; Emetics; Vomiting
PubMed: 37863383
DOI: 10.1016/j.fct.2023.114068 -
Cureus Dec 2023Belly dancer's dyskinesia (BDD) is an unusual neurological disorder characterized by focal dyskinesia that results in involuntary, rhythmic movements of the anterior...
Belly dancer's dyskinesia (BDD) is an unusual neurological disorder characterized by focal dyskinesia that results in involuntary, rhythmic movements of the anterior abdominal wall. This case report comprehensively examines the presentation, potential medication-induced etiology, and therapeutic response of a 64-year-old male diagnosed with schizophrenia. The patient developed BDD-like symptoms resembling hiccups, experiencing recurrent episodes that endured for hours and occurred nearly daily, significantly affecting wakefulness and sleep. Importantly, the patient's medical history included the utilization of fluphenazine and benztropine for schizophrenia management. Following a thorough multidisciplinary neurology consultation, a tailored treatment regimen involving clonazepam, promethazine, and baclofen was initiated, culminating in a noteworthy reduction in symptom frequency. This report substantially enriches the existing knowledge of BDD, highlighting the critical necessity to elucidate its intricate pathophysiology for the advancement of refined diagnostic and therapeutic strategies.
PubMed: 38161556
DOI: 10.7759/cureus.49796 -
Spectrochimica Acta. Part A, Molecular... Jun 2024In the current work, sulfur and nitrogen co-doped carbon dots (S,N-CDs) as simple, sensitive, and selective turn-off fluorescent nanosensors were utilized for analysis...
In the current work, sulfur and nitrogen co-doped carbon dots (S,N-CDs) as simple, sensitive, and selective turn-off fluorescent nanosensors were utilized for analysis of three phenothiazine derivatives, including acetophenazine (APZ), chlorpromazine (CPH), and promethazine (PZH). S,N-CDs were synthesized through a green one-pot microwave-assisted technique using widely available precursors (thiourea and ascorbic acid). HRTEM, EDX, FTIR spectroscopy, UV-Vis absorption spectroscopy, and fluorescence spectroscopy were used to characterize the as-synthesized CDs. When excited at 330 nm, the carbon dots produced a maximum emission peak at 410 nm. The cited drugs statically quenched the S,N-CDs fluorescence as revealed by the Stern-Volmer equation. The current method represents the first spectrofluorimetric approach for the determination of the studied drugs without the need for chemical derivatization or harsh reaction conditions. The importance of the proposed work is magnified as the cited drugs do not have any fluorescent properties. The fluorescence of the developed sensor exhibited a linear response to APZ, CPH, and PZH in the concentration ranges of 5.0-100.0, 10.0-100.0, and 10.0-200.0 μM with detection limits of 1.53, 1.66, and 2.47 μM, respectively. The developed fluorescent probes have the advantages of rapidity and selectivity for APZ, CPH, and PZH analysis in tablets with acceptable % recoveries of (98.06-101.66 %). Evaluation of the method's greenness was performed using the Complementary Green Analytical Procedure Index (ComplexGAPI) and Analytical GREEnness metric (AGREE) metrics, indicating that the method is environmentally friendly. Validation of the proposed method was performed according to ICHQ2 (R1) guidelines.
Topics: Fluorescent Dyes; Quantum Dots; Phenothiazines; Antipsychotic Agents; Carbon; Nitrogen; Sulfur
PubMed: 38554691
DOI: 10.1016/j.saa.2024.124207 -
Frontiers in Nutrition 2024To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs.
BACKGROUND
To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs.
METHODS
Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the "most significant trait-related genes" (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells.
RESULTS
Lipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells.
CONCLUSION
This study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.
PubMed: 38595789
DOI: 10.3389/fnut.2024.1381779 -
Langmuir : the ACS Journal of Surfaces... Aug 2023In the realm of electrochemical sensor application, the development and fabrication of semiconducting metal oxides with the integration of conducting polymers for the...
CdO Decorated with Polypyrrole Nanotube Heterostructure: Potent Electrocatalyst for the Detection of Antihistamine Drug Promethazine Hydrochloride in Environmental Samples.
In the realm of electrochemical sensor application, the development and fabrication of semiconducting metal oxides with the integration of conducting polymers for the trace-level detection of pharmaceutical medicines garnered considerable interest. Herein, we reported facile cadmium oxide decorated with polypyrrole nanotubes fabricated on a glassy carbon electrode (CdO@PPy/GCE) for efficient determination of antihistamine drug promethazine hydrochloride (PMH). The as-synthesized CdO@PPy composite was characterized by various analytical tools like X-ray powder diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Furthermore, the electrocatalytic activity of the modified electrode for PMH detection was examined by voltammetry and amperometric methods, and the modified electrode exhibited lower charge transfer resistance compared to the bare GCE. Under the optimized condition, the fabricated electrode shows a wide linear range (50-550 μM), better sensitivity (0.13 μAμM cm), low detection limit (10.83 nM) (S/N = 3), and excellent selectivity and reproducibility toward PMH detection. Moreover, the modified GCE depicted eminent practical ability for PMH detection in lake water and pharmaceutical tablets.
Topics: Polymers; Promethazine; Pyrroles; Reproducibility of Results; Nanotubes; Histamine Antagonists; Pharmaceutical Preparations; Electrodes; Limit of Detection
PubMed: 37490749
DOI: 10.1021/acs.langmuir.3c01445 -
Psychopharmacology May 2024Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies...
RATIONALE
Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined.
OBJECTIVES
To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients.
METHODS
We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors.
RESULTS
Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (β = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (β = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction.
CONCLUSIONS
This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.
PubMed: 38733528
DOI: 10.1007/s00213-024-06603-y -
Food Chemistry Jun 2024The prohibition of antipsychotic drugs in animal foodstuffs has raised significant concerns. In this study, a novel matrix purification adsorbent comprising a polymer...
The prohibition of antipsychotic drugs in animal foodstuffs has raised significant concerns. In this study, a novel matrix purification adsorbent comprising a polymer (polyaniline and polypyrrole)-functionalized melamine sponge (Ms) was employed for the high performance liquid chromatography-diode array detector (HPLC-DAD) detection of three phenothiazines (chlorpromazine, thioridazine, and promethazine), and a tricyclic imipramine in milk. The as-prepared functionalized Ms was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle measurements. Excellent linearity with a coefficient of determination (R) of 0.999 was achieved for all drugs within the concentration range of 0.01-47.00 μg mL. The recoveries of the four analytes ranged from 92.1 % to 106.9 % at the three spiked levels. These results demonstrate the successful application of the proposed method for the determination of the four drugs. Cost-effective polymer-functionalized Ms is a viable alternative for matrix purification, enabling rapid determination of drug residues in diverse food samples.
Topics: Animals; Milk; Antipsychotic Agents; Chromatography, High Pressure Liquid; Polymers; Pyrroles; Solid Phase Extraction; Triazines
PubMed: 38309075
DOI: 10.1016/j.foodchem.2024.138553 -
Biomedicines Aug 2023Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for the treatment of COVID-19, which is metabolized to...
Development and Validation of a High-Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS/MS) Method for Quantification of Major Molnupiravir Metabolite (β-D-N4-hydroxycytidine) in Human Plasma.
Molnupiravir is an antiviral drug against viral RNA polymerase activity approved by the FDA for the treatment of COVID-19, which is metabolized to β-D-N4-hydroxycytidine (NHC) in human blood plasma. A novel method was developed and validated for quantifying NHC in human plasma within the analytical range of 10-10,000 ng/mL using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) to support pharmacokinetics studies. For sample preparation, the method of protein precipitation by acetonitrile was used, with promethazine as an internal standard. Chromatographic separation was carried out on a Shim-pack GWS C18 (150 mm × 4.6 mm, 5 μm) column in a gradient elution mode. A 0.1% formic acid solution in water with 0.08% ammonia solution (eluent A, /) and 0.1% formic acid solution in methanol with 0.08% ammonia solution mixed with acetonitrile in a 4:1 ratio (eluent B, /) were used as a mobile phase. Electrospray ionization (ESI) was used as an ionization source. The developed method was validated in accordance with the Eurasian Economic Union (EAEU) rules, based on the European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines for the following parameters and used within the analytical part of the clinical study of molnupiravir drugs: selectivity, suitability of standard sample, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification (LLOQ), carryover, and stability.
PubMed: 37760797
DOI: 10.3390/biomedicines11092356 -
Frontiers in Pharmacology 2023The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during...
The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic. We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine. In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries ( = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information. Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation.
PubMed: 38094894
DOI: 10.3389/fphar.2023.1238875 -
Journal of the American Society of... Jun 2024In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk. Analyses...
KEY POINTS
In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk. Analyses considering additional cardiac outcomes had consistent findings.
BACKGROUND
Individuals receiving hemodialysis have a high incidence of sudden cardiac death and are susceptible to QT interval–prolonging medication–related cardiac complications. Ondansetron, an antiemetic with known QT-prolonging potential, is associated with fatal arrhythmias in the general population when administered intravenously. The cardiac safety of ondansetron in the hemodialysis population is unknown.
METHODS
We conducted a new-user, active-comparator, cohort study using United States Renal Data System data (2012–2019) to examine the association between the initiation of oral ondansetron versus antiemetics with lesser QT-prolonging potential (promethazine, metoclopramide, or prochlorperazine) and the 10-day risk of sudden cardiac death among individuals receiving hemodialysis. We used inverse probability of treatment-weighted survival models to estimate adjusted hazard ratios, risk differences, and 95% confidence intervals (CIs). We used an intention-to-treat approach in which non-sudden cardiac death was considered a competing event. We examined additional cardiac outcomes in secondary analyses.
RESULTS
Of 119,254 study patients, 64,978 (55%) initiated ondansetron and 54,276 (45%) initiated a comparator antiemetic. Initiation of ondansetron versus a comparator antiemetic was associated with higher relative and absolute 10-day risks of sudden cardiac death (adjusted hazard ratio, 1.44 [95% CI, 1.08 to 1.93]; adjusted risk difference, 0.06% [95% CI, 0.01% to 0.11%]). The number needed to harm was 1688. Analyses of additional cardiac outcomes yielded similar findings.
CONCLUSIONS
Compared with initiation of antiemetics with lesser QT-prolonging potential, initiation of ondansetron was associated with higher short-term cardiac risks among people receiving hemodialysis.
Topics: Humans; Renal Dialysis; Death, Sudden, Cardiac; Ondansetron; Male; Female; Middle Aged; Kidney Failure, Chronic; Antiemetics; Aged
PubMed: 38409683
DOI: 10.1681/ASN.0000000000000336