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Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
Journal of Applied Toxicology : JAT Apr 2023In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the... (Review)
Review
In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.
Topics: Animals; Antipsychotic Agents; Zebrafish; Promazine; Phenothiazines; Chlorpromazine; Mammals
PubMed: 36165981
DOI: 10.1002/jat.4397 -
Journal of Biomolecular NMR Jul 2021We used NMR to show that the antipsychotic phenothiazine drugs promazine and promethazine bind to GDP-KRAS. Promazine also binds to oncogenic GDP-KRAS(G12D), and to wild...
We used NMR to show that the antipsychotic phenothiazine drugs promazine and promethazine bind to GDP-KRAS. Promazine also binds to oncogenic GDP-KRAS(G12D), and to wild type GppNHp-KRAS. A panel of additional phenothiazines bind to GDP-KRAS but with lower affinity than promazine or promethazine. Binding is most dependent on substitutions at C-2 of the tricyclic phenothiazine ring. Promazine was used to generate an NMR-driven HADDOCK model of the drug/GDP-KRAS complex. The structural model shows the tricyclic phenothiazine ring of promazine associates with the hydrophobic pocket p1 that is bordered by the central β sheet and Switch II in KRAS. Binding appears to stabilize helix 2 in a conformation that is similar to that seen in KRAS bound to other small molecules. Association of phenothiazines with KRAS may affect normal KRAS signaling that could contribute to multiple biological activities of these antipsychotic drugs. Moreover, the phenothiazine ring represents a new core scaffold on which to design modulators of KRAS activity.
Topics: Amino Acid Substitution; Antipsychotic Agents; Humans; Models, Molecular; Mutation, Missense; Nuclear Magnetic Resonance, Biomolecular; Phenothiazines; Protein Binding; Protein Conformation, beta-Strand; Proto-Oncogene Proteins p21(ras)
PubMed: 34176062
DOI: 10.1007/s10858-021-00371-z -
Contact Dermatitis Jun 2022
Topics: Dermatitis, Allergic Contact; Dermatitis, Photoallergic; Humans; Patch Tests; Promazine; Ultraviolet Rays
PubMed: 35195295
DOI: 10.1111/cod.14086 -
Chemosphere Oct 2022Water pollution has significant impact on water usage, and various contaminants, such as organic and inorganic compounds, heavy metals, dyes, pharmaceuticals compounds,... (Review)
Review
Water pollution has significant impact on water usage, and various contaminants, such as organic and inorganic compounds, heavy metals, dyes, pharmaceuticals compounds, pathogens and radioactive compounds, are implicated. The quest for globalisation, structural developments and other related anthropogenic activities promote the release of contaminants that induce water pollution. Hence, treatment and remediation options that can remove pollutants from watercourses and wastewater have been developed. Applied nanotechnology using carbon nanocomposites has recently drawn attention because it has the advantages of low preparation cost, high surface area, pore volume and environmental stability. Magnetic carbon nanocomposites usually exhibit excellent performance in adsorbing contaminants from aqueous solutions, and thus expanding the use of nanotechnology in water treatment is of great importance. Therefore, this review explores the geographical outlook of water pollution, sources of water pollution and types of contaminants found in water and discusses the use of carbon nanocomposites as an emerging sustainable technology for water pollutant removal. The various properties of carbon-based composites influence the extent of pollutant adsorption during water treatment processes. Most carbon-based nanocomposites are generated from biomass produced by agro-waste materials. Magnetic activated carbon nanocomposites produced from walnut shells and rice husk waste can remove 78% of Cd(II) from contaminated aqueous systems. Magnetic nanocomposites from peanut shell, tea waste, curcumin nanoparticles, sunflower head waste, rice husk, hydrophyte biomass, palm waste and sugarcane bagasse facilitate hydrothermal carbonisation, chemical precipitation, co-precipitation, chemical activation, calcination and fast pyrolysis. These nanocomposites have benefitted wastewater treatment by increasing efficiency in removing pharmaceutical, dye and organic contaminants, such as promazine, ciprofloxacin, amoxicillin, rhodamine 6G, methyl blue, phenol and phenanthrene. Hence, this review discusses the relatively low costs, good biocompatibility, large surface-to-volume ratio, magnetic separation capability and reusability carbon materials and highlights the advantages of using magnetic carbon nanocomposites in the removal of contaminants from water or wastewater through adsorption mechanisms.
Topics: Adsorption; Cellulose; Coloring Agents; Environmental Pollutants; Magnetic Phenomena; Nanocomposites; Saccharum; Wastewater; Water Pollutants, Chemical; Water Purification
PubMed: 35724716
DOI: 10.1016/j.chemosphere.2022.135384 -
International Journal of Molecular... Apr 2022The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide...
The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer's disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of Aβ aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit Aβ aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential.
Topics: Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Endothelial Cells; Hemolysis; Humans; Quetiapine Fumarate; Rivastigmine
PubMed: 35563011
DOI: 10.3390/ijms23094621 -
Environmental Science and Pollution... Jul 2023This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar...
Competitive adsorptive removal of promazine and promethazine from wastewater using olive tree pruning biochar: operational parameters, kinetics, and equilibrium investigations.
This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar (BC-OTPR). The impact of individual and combinatory effects of operational variables was evaluated for the first time using central composite design (CCD). Simultaneous removal of both drugs was maximized utilizing the composite desirability function. At low concentrations, the uptake of PRO and PMT from their individual solutions was achieved with high efficiency of 98.64%, 47.20 mg/g and 95.87%, 38.16 mg/g, respectively. No major differences in the removal capacity were observed for the binary mixtures. Characterization of BC-OTPR confirmed successful adsorption and showed that the OTPR surface was predominantly mesoporous. Equilibrium investigations revealed that the Langmuir isotherm model best describes the sorption of PRO/PMT from their individual solutions with maximum adsorption capacities of 640.7 and 346.95 mg/g, respectively. The sorption of PRO/PMT conforms to the pseudo-second-order kinetic model. Regeneration of the adsorbent surface was successfully done with desorption efficiencies of 94.06% and 98.54% for PRO and PMT, respectively, for six cycles.
Topics: Wastewater; Promethazine; Olea; Promazine; Kinetics; Adsorption; Charcoal; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37326738
DOI: 10.1007/s11356-023-27688-6 -
Spectrochimica Acta. Part A, Molecular... Feb 2021Detection and qualification process related to impurities assume importance in pharmacological drug development programmes and the present article gives the structural...
Detection and qualification process related to impurities assume importance in pharmacological drug development programmes and the present article gives the structural and spectral characterisation of phenothiazine derivatives, promazine (PME) and trifluoperazine (TPE) and their self-assembly with graphene/fullerene/carbon ring (CG/CF/CR) systems theoretically. The investigation of adsorption behaviour of these compounds can provide valuable information about its reactivity, electronic and structural properties. Three-dimensional electrostatic potential diagrams were mapped. The frontier orbital energies and energy band gaps of the molecules were computed. Delocalization of charge density between the bonding or lone pair and antibonding orbitals is calculated by NBO analysis. Docking was executed to investigate binding areas of chemical compounds. Bioactivity scores show that the pharmacokinetic and pharmacological properties of the ligands are appropriate leading to be considered potential drug agents. The obtained theoretical wavenumber results of the present study were fully compatible with the experimental results.
Topics: Adsorption; Fullerenes; Graphite; Promazine; Psychotropic Drugs; Quantum Theory; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Trifluoperazine
PubMed: 33039847
DOI: 10.1016/j.saa.2020.119012 -
Journal of Analytical Toxicology Apr 2023The use of dried urine spots (DUS) can simplify sample handling, shipment and storage when compared to liquid urine samples. To prepare DUS, a small amount of urine is...
The use of dried urine spots (DUS) can simplify sample handling, shipment and storage when compared to liquid urine samples. To prepare DUS, a small amount of urine is pipetted on a filter paper card. The subsequent drying of the specimen can prevent the post-sampling formation or degradation of substances (e.g., caused by bacteria). To evaluate the potential of DUS screening, 17 authentic urine samples, containing a broad range of substances, were extracted and analyzed on a Sciex TripleTOF® 5600+ System using a non-targeted screening and library searching approach. The screening results were compared to the analysis of the same urine sample in liquid form, using the same high-resolution liquid chromatography--quadrupole time-of-flight mass spectrometry method. More than 65 different legal and illegal drugs were successfully identified within the investigated 17 urine samples using the DUS screening approach. When compared to the analysis of liquid urine, the following compounds could not be identified: 1x ecgonine methyl ester, 1x nicotine, 1x promazine and 1x 11-nor-9-carboxy-∆9-tetrahydrocannabinol. Overall, 95.2% of the target substances that have been detected in liquid urine were identified correctly using the DUS approach. In conclusion, DUS screening offers a simple, cost-effective and easier sample handling alternative to the traditional use of liquid urine and provides the detection of the most important substances for forensic requirements. Furthermore, the DUS sample preparation can be fully automated (sample documentation, internal standard application and extraction).
Topics: Drug Evaluation, Preclinical; Body Fluids; Mass Spectrometry; Chromatography, Liquid; Specimen Handling
PubMed: 36722166
DOI: 10.1093/jat/bkad007 -
Talanta Dec 2019Monodisperse molecularly imprinted polymers (MIPs) for promazine derivatives [promazine (PZ), methylpromazine (MPZ), chlorpromazine (CPZ) and bromopromazine (BPZ)], MIP,...
Monodisperse molecularly imprinted polymers (MIPs) for promazine derivatives [promazine (PZ), methylpromazine (MPZ), chlorpromazine (CPZ) and bromopromazine (BPZ)], MIP, MIP, MIP and MIP, were prepared using methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate as a crosslinker by multi-step swelling and polymerization. The retention and molecular-recognition properties of the obtained MIPs were evaluated using LC in hydrophilic interaction chromatography (HILIC) and reversed-phase modes. In computational approaches, intermolecular interaction modes and energies between PZ derivatives and MAAs were evaluated at the HF/6-311G(d,p) level. The interaction energies of PZ, MPZ, CPZ and BPZ with 4 equivalents of MAAs were calculated. The results indicated that the interaction of the aliphatic amine moiety of a PZ derivative with MAA gave almost similar interaction energies at the HF/6-311G(d,p) level, and that the interaction of the sulfur atom of a phenothiazine scaffold with MAA was also the case. The third interaction of the aromatic amine of a PZ derivative with MAA was in the order of MPZ > PZ > CPZ > BPZ presumably due to the change of basicity by the electron-donating or electron-withdrawing effect of a subsituent. Furthermore, the fourth attractive modes of CPZ and BPZ were suggested to be the interaction of their halogen atoms with MAA through both halogen bonding and hydrogen bonding, while PZ and MPZ were suggested to have the weak C-H ⋅⋅⋅ π interaction with MAA. In HILIC mode, the interaction energies at the HF method had good correlation with the retention factor of a PZ derivative on each MIP, indicating that in addition to the shape recognition, the attractive electrostatic interactions would be more responsible for its retention rather than the dispersion energies. Furthermore, in addition to the shape recognition, ionic and hydrophobic interactions, and halogen bonding and hydrogen bonding (the last interaction seems to be weak) seem to work for the retention and molecular-recognition of PZ derivatives on the MIPs in reversed-phase mode.
PubMed: 31450460
DOI: 10.1016/j.talanta.2019.120149