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Biosensors Oct 2022Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable...
Despite all the psychological advantages of alprazolam, its long list of toxic properties and interactions has caused concern and highlighted the need for a reliable sensing method. In this study, we developed a simple, highly sensitive electrochemical nanobiosensor to determine the desirable dose of alprazolam, averting the undesirable consequences of overdose. Gold nanourchins (AuNUs) and iron-nickel reduced graphene oxide (Fe-Ni@rGO) were immobilized on a glassy carbon electrode, which was treated beforehand. The electrode surface was characterized using cyclic voltammetry, Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, and differential pulse voltammetry. The fabricated sensor showed two linear ranges (4 to 500 µg L and 1 to 50 mg L), low limit of detection (1 µg L), high sensitivity, good repeatability, and good recovery. Increased -OH and carboxyl (-COOH) groups on the electrode surface, resulting in improved the adsorption of alprazolam and thus lower limit of detection. This nanobiosensor could detect alprazolam powder dissolved in diluted blood serum; we also studied other benzodiazepine drugs (clonazepam, oxazepam, and diazepam) with this nanobiosensor, and results were sensible, with a significant difference.
Topics: Alprazolam; Graphite; Nanocomposites; Gold; Electrodes; Electrochemical Techniques
PubMed: 36354454
DOI: 10.3390/bios12110945 -
Psychoactive drugs: occurrence in aquatic environment, analytical methods, and ecotoxicity-a review.Environmental Science and Pollution... Nov 2017This review focused on seven psychoactive drugs being six benzodiazepines (alprazolam, bromazepam, clonazepam, diazepam, lorazepam, and oxazepam) and one antidepressant... (Review)
Review
This review focused on seven psychoactive drugs being six benzodiazepines (alprazolam, bromazepam, clonazepam, diazepam, lorazepam, and oxazepam) and one antidepressant (citalopram) widely consumed by modern society and detected in different aqueous matrices (drinking water, surface water, groundwater, seawater, estuary water, influent and effluent of wastewater treatment plants). The review included 219 selected scientific papers from which 1642 data/entries were obtained, each entry corresponding to one target compound in one aqueous matrix. Concentrations of all investigated drugs in all aqueous matrices varied from 0.14 to 840,000 ng L. Citalopram presented the highest concentrations in the aqueous matrices. Based on the Wilcoxon-Mann-Whitney test, differences between wastewater influents and effluents were not significant for most wastewater categories, suggesting that conventional wastewater treatment systems as such do not remove or remove partially these compounds. High-income countries showed much lower concentrations in surface water than the group formed by upper-middle-, lower-middle-, and low-income countries. Regarding analytical methods, solid-phase extraction (SPE) was by far the most used extraction method (83%) and performance liquid chromatography (HPLC) (73%) coupled to mass spectrometry (99%) the most common analytical method. Changes in behavior and in survival rates were the most common effects reported on bioindicators (aquatic species) due to the presence of these drugs in water. Concentrations of psychoactive drugs found in surface waters were most of the time within the range that caused measurable toxic effects in ecotoxicity assays.
Topics: Chromatography, High Pressure Liquid; Environmental Monitoring; Mass Spectrometry; Psychotropic Drugs; Solid Phase Extraction; Wastewater; Water Pollutants, Chemical
PubMed: 28942593
DOI: 10.1007/s11356-017-0170-4 -
Psychopharmacology Apr 2018Screening of drug-induced performance impairment is needed to provide meaningful information for users and prescribers regarding the impact of drugs on driving. The main... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Screening of drug-induced performance impairment is needed to provide meaningful information for users and prescribers regarding the impact of drugs on driving. The main objective was to assess the effects of oxazepam 10 mg (OXA10), oxazepam 30 mg (OXA30), and diazepam 10 mg (DIA10) on standard deviation of lateral position (SDLP) in a highway driving test in actual traffic and to determine the ability of eight neurocognitive tests to detect comparable effects.
METHODS
Twenty-three healthy volunteers participated in a four-way double-blind, placebo-controlled, crossover study. The highway driving test was conducted between 4 and 5 h after drug intake. A range of neurocognitive tests was conducted before and after driving, 2 and 6 h post-treatment, respectively.
RESULTS
Mean SDLP increased by 1.83, 3.03, and 7.57 cm after OXA10, DIA10, and OXA30, respectively. At 2 h post-treatment, all neurocognitive tests, except the useful field of view, showed performance impairment in all active treatments. Effect sizes (ES) were moderate for OXA10, large ES for DIA10, and largest ES for OXA30. Modest correlations were found between changes in SDLP and performance in the attention network test (ANT), the divided attention test (DAT), and the psychomotor vigilance test (PVT).
CONCLUSION
OXA10 caused minor, DIA10 moderate, and OXA30 severe driving impairment. No neurocognitive test was both dose dependently sensitive and able to be associated with driving impairment. No neurocognitive test can replace the on-the-road highway driving test.
Topics: Adult; Attention; Automobile Driving; Cognition; Cross-Over Studies; Diazepam; Double-Blind Method; Female; Healthy Volunteers; Humans; Hypnotics and Sedatives; Male; Mental Status and Dementia Tests; Middle Aged; Oxazepam; Psychomotor Performance; Young Adult
PubMed: 29500585
DOI: 10.1007/s00213-018-4844-5 -
Philosophical Transactions of the Royal... Nov 2014The study of animal behaviour is important for both ecology and ecotoxicology, yet research in these two fields is currently developing independently. Here, we... (Review)
Review
The study of animal behaviour is important for both ecology and ecotoxicology, yet research in these two fields is currently developing independently. Here, we synthesize the available knowledge on drug-induced behavioural alterations in fish, discuss potential ecological consequences and report results from an experiment in which we quantify both uptake and behavioural impact of a psychiatric drug on a predatory fish (Perca fluviatilis) and its invertebrate prey (Coenagrion hastulatum). We show that perch became more active while damselfly behaviour was unaffected, illustrating that behavioural effects of pharmaceuticals can differ between species. Furthermore, we demonstrate that prey consumption can be an important exposure route as on average 46% of the pharmaceutical in ingested prey accumulated in the predator. This suggests that investigations of exposure through bioconcentration, where trophic interactions and subsequent bioaccumulation of exposed individuals are ignored, underestimate exposure. Wildlife may therefore be exposed to higher levels of behaviourally altering pharmaceuticals than predictions based on commonly used exposure assays and pharmaceutical concentrations found in environmental monitoring programmes.
Topics: Animals; Anti-Anxiety Agents; Odonata; Oxazepam; Perches; Predatory Behavior; Water Pollutants, Chemical
PubMed: 25405968
DOI: 10.1098/rstb.2013.0580 -
Chemosphere Jun 2017Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about...
Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about their occurrence in European surface waters. Benzodiazepines, a class of pharmaceuticals with anxiolytic properties, have received interest due to their behavioral modifying effect on exposed biota. In this study, our results show the presence of one or more benzodiazepine(s) in 86% of the analyzed surface water samples (n = 138) from 30 rivers, representing seven larger European catchments. Of the 13 benzodiazepines included in the study, we detected 9, which together showed median and mean concentrations (of the results above limit of quantification) of 5.4 and 9.6 ng L, respectively. Four benzodiazepines (oxazepam, temazepam, clobazam, and bromazepam) were the most commonly detected. In particular, oxazepam had the highest frequency of detection (85%) and a maximum concentration of 61 ng L. Temazepam and clobazam were found in 26% (maximum concentration of 39 ng L) and 14% (maximum concentration of 11 ng L) of the samples analyzed, respectively. Finally, bromazepam was found only in Germany and in 16 out of total 138 samples (12%), with a maximum concentration of 320 ng L. This study clearly shows that benzodiazepines are common micro-contaminants of the largest European river systems at ng L levels. Although these concentrations are more than a magnitude lower than those reported to have effective effects on exposed biota, environmental effects cannot be excluded considering the possibility of additive and sub-lethal effects.
Topics: Benzodiazepines; Clobazam; Environmental Monitoring; Europe; Oxazepam; Rivers; Temazepam; Water Pollutants, Chemical
PubMed: 28273540
DOI: 10.1016/j.chemosphere.2017.02.126 -
Analytical and Bioanalytical Chemistry Jan 2022Oxazepam, one of the most frequently prescribed anxiolytic drugs, is not completely removed from wastewater with conventional treatment processes. It can thus be found...
Oxazepam, one of the most frequently prescribed anxiolytic drugs, is not completely removed from wastewater with conventional treatment processes. It can thus be found at trace levels in environmental water, with human urine constituting the major source of contamination. This study focused on the development and characterization of molecularly imprinted polymers (MIPs) for the selective solid-phase extraction of oxazepam at trace levels from environmental water and human urine samples. Two MIPs were synthesized, and their selectivity in pure organic and aqueous media were assayed. After optimizing the extraction procedure adapted to a large sample volume to reach a high enrichment factor, the most promising MIP was applied to the selective extraction of oxazepam from environmental water. Extraction recoveries of 83 ± 12, 92 ± 4 and 89 ± 10% were obtained using the MIP for tap, mineral and river water, respectively, while a recovery close to 40% was obtained on the corresponding non-imprinted polymer (NIP). Thanks to the high enrichment factors, a limit of quantification (LOQ) of 4.5 ng L was obtained for river water. A selective extraction procedure was also developed for urine samples and gave rise to extraction recoveries close to 95% for the MIP and only 23% for the NIP. Using the MIP, a LOQ of 357 ng L was obtained for oxazepam in urine. The use of the MIP also helped to limit the matrix effects encountered for the quantification of oxazepam in environmental samples and in human urine samples after extraction on an Oasis HLB sorbent.
Topics: Chromatography, High Pressure Liquid; Humans; Molecular Imprinting; Molecularly Imprinted Polymers; Oxazepam; Polymers; Solid Phase Extraction
PubMed: 33751162
DOI: 10.1007/s00216-021-03268-w -
The AAPS Journal Oct 2020Physiologically based pharmacokinetic (PBPK) modeling is less well established for substrates of UDP-glucuronosyltransferases (UGT) than for cytochrome P450 (CYP)...
Construction and Verification of Physiologically Based Pharmacokinetic Models for Four Drugs Majorly Cleared by Glucuronidation: Lorazepam, Oxazepam, Naloxone, and Zidovudine.
Physiologically based pharmacokinetic (PBPK) modeling is less well established for substrates of UDP-glucuronosyltransferases (UGT) than for cytochrome P450 (CYP) metabolized drugs and more verification of simulations is necessary to increase confidence. To address specific challenges of UGT substrates, we developed PBPK models for four drugs cleared majorly via glucuronidation (lorazepam, oxazepam, naloxone, and zidovudine). In vitro to in vivo scaling of intrinsic clearance generated with co-cultured human hepatocytes was applied for hepatic metabolism and extra-hepatic clearance was extrapolated based on relative expression of UGT isoforms in the liver, kidney, and intestine. Non-metabolic clearance and the contributions of individual UGT isoforms to glucuronidation were based on in vitro and in vivo studies taken from the literature and simulations were verified and evaluated with a broad set of clinical pharmacokinetic data. Model evaluation showed systemic clearance predictions within 1.5-fold for all drugs and all simulated parameters were within 2-fold of observed. However, during the verification step, top-down model fitting was necessary to adjust for under-prediction of zidovudine V and renal clearance and over estimation of intestinal first pass for lorazepam, oxazepam, and zidovudine. The impact of UGT2B15 polymorphisms on the pharmacokinetics of oxazepam and lorazepam was simulated and glucuronide metabolites were also simulated for all four drugs. To increase confidence in predicting extra-hepatic clearance, improvement of enzyme phenotyping for UGT substrates and more quantitative tissue expression levels of UGT enzymes are both needed. Prediction of glucuronide disposition is also challenging when active transport processes play a major role.
Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Cell Culture Techniques; Cells, Cultured; Coculture Techniques; Datasets as Topic; Female; Glucuronides; Glucuronosyltransferase; Hepatocytes; Humans; Intestines; Kidney; Liver; Lorazepam; Male; Metabolic Clearance Rate; Microsomes, Liver; Middle Aged; Models, Biological; Naloxone; Oxazepam; Young Adult; Zidovudine
PubMed: 33033903
DOI: 10.1208/s12248-020-00513-5 -
Pharmaceutics Feb 2024Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and...
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected K (K) values and predict the area under the concentration-time curve ratio (AUCR). The estimated K values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the K values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug-drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered.
PubMed: 38399297
DOI: 10.3390/pharmaceutics16020243 -
Journal of Analytical Toxicology Sep 2016To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because... (Review)
Review
To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases.
Topics: Alprazolam; Blood-Brain Barrier; Bromazepam; Chlordiazepoxide; Diazepam; Forensic Toxicology; Humans
PubMed: 27416838
DOI: 10.1093/jat/bkw059 -
Journal of Psychosocial Nursing and... May 2016Distinguishing itself from other benzodiazepine drugs, oxazepam has an interesting pharmacological and clinical profile, including binding effects on the translocator...
Distinguishing itself from other benzodiazepine drugs, oxazepam has an interesting pharmacological and clinical profile, including binding effects on the translocator protein (TSPO) and a relatively favorable safety and abuse liability profile. TSPO is found in the brain (where it is involved in neurosteroid synthesis), but is also expressed in the heart and other peripheral tissues. Oxazepam is potentially useful in the treatment of substance abuse, especially in conjunction with the cortisol synthesis inhibitor metyrapone, and can be considered an appropriate medication to use in the treatment of depression. The oxazepam/metyrapone combination has been piloted in cocaine-dependent patients and should be investigated in patients with depression. Expression of cardiac TSPO is altered by different stress conditions, and drugs binding to TSPO may have cardioprotective effects. The possibility of oxazepam, alone or together with antidepressant drugs, having a positive effect on cardiac function in patients with depression should also be studied. [Journal of Psychosocial Nursing and Mental Health Services, 54(5), 21-24.].
Topics: Depression; Humans; Hypnotics and Sedatives; Oxazepam; Substance-Related Disorders
PubMed: 27135891
DOI: 10.3928/02793695-20160420-03