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Benzodiazepine ingestion is frequent in patients admitted to ICU for intoxications. Generally, a supportive approach by securing the airway, breathing, and circulation is sufficient. Flumazenil is a well-known antidote for benzodiazepines but does not influence its elimination. Following preclinical data, we applied for the first time in humans a hemadsorption filter in a patient with a bromazepam intoxication. This technique proved to be effective in eliminating bromazepam in a patient with CHILD-C cirrhosis. We conclude that hemadsorption is a viable option to reduce length of ICU stay or intubation in slow metabolizers without contraindications.

Benzodiazepine ingestion is frequent in patients admitted to ICU for intoxications. Generally, a supportive approach by securing the airway, breathing, and circulation is sufficient. Flumazenil is a well-known antidote for benzodiazepines but does not influence its elimination. Following preclinical data, we applied for the first time in humans a hemadsorption filter in a patient with a bromazepam intoxication. This technique proved to be effective in eliminating bromazepam in a patient with CHILD-C cirrhosis. We conclude that hemadsorption is a viable option to reduce length of ICU stay or intubation in slow metabolizers without contraindications. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the sensitivity and selectivity of ultra-performance liquid chromatographic (UPLC) quantification of bromazepam (BRZ) and diazepam (DZP) in pharmaceutical industrial wastewater. Methods: Wastewater samples were collected from the effluents of a pharmaceutical industrial plant producing BRZ and DZP in tablet dosage forms. The quantification of BRZ and DZP was done after their solid-phase extraction. The resolution process was performed on WatersTM column as the stationary phase. The mobile phase was acetonitrile: methanol: 0.05 M phosphate buffer (pH 6.5), at a volume ratio of 5:2:3, with a flow rate of 0.7 mL/min. Detection was carried out at 240 nm in a concentration range of 10 - 250 ng/mL. The method was fully validated in line with ICH-Q2B regulations. Results: The UPLC method was validated for the quantification of BRZ and DZP. The relative percentage recoveries were 99.55 ± 0.48 (n = 5) and 101.34 ± 0.86 (n = 5), for BRZ and DZP, respectively, in spiked distilled water, and 99.16 ± 0.77 (n = 5) and 99.32 ± 0.56 (n = 5), in tap water, respectively. The UPLC revealed effluent content ranging from 20.68 - 44.77 mg/mL for BRZ and 22.77 - 41.83 ng/mL for DZP. These values were not significantly different from their reference standards (p > 0.05). Conclusion: A sensitive and selective UPLC-method has been developed for the reproducible determination of BRZ and DZP in industrial wastewater samples. The effective monitoring of the pharmaceutical industrial pollutant will help to conserve the environment and minimize the hazardous effects of these pollutants. [ABSTRACT FROM AUTHOR]

The application of ion-selective electrodes (ISEs) in the detection and determination of environmental pollutants has become a very important mission in the last few years. Two selective and sensitive membrane electrodes were fabricated in the laboratory and intended to evaluate the electrochemical response of bromazepam (BRZ) using phosphotungstic acid (PTA) and sodium tetraphenylborate (TPB) as ion pairing agents. The linearity range of the fabricated electrodes was between 1 × 10−6 M to 1 × 10−3 M. Nernstian slopes of 54 mV/decade and 57 mV/decade were obtained for the BRZ-PTA and BRZ-TPB membrane electrodes, respectively. The performance of the fabricated membranes was optimum in the pH range of 3–6. Optimum electrochemical response was attained through the careful adjustment of all assay settings. The cited method was successfully applied for the selective determination of BRZ in either its pure form or real wastewater samples obtained from a pharmaceutical industrial plant. The main core of novelty in the suggested method lies in the application of the membranes for the sensitive, selective, and economic determination of BRZ in real wastewater effluents without the tedious sample pretreatment procedures. This can make the suggested method considered an eco-friendly method, as it minimizes the use of organic solvents and chemicals used in the pretreatment process.

Similar to the antibiotic mixing strategies, which depend on reducing the worth of diffusion of the resistant bacteria to new host, in this contribution, we explicit new mixed‐ligand complexes of the type [M(SMZ)2(BZM)] (M = Co(II), Ni(II) and Cu(II)) based on two drugs: sulfamethazine (SMZ) and bromazepam (BZM). The novelty aspect of the present work relies on combining two drugs in a single molecule via the synthesis of the ternary complexes. The ternary complexes were characterized by spectroscopic and analytical tools with the aid of the quantum chemical calculations. Copper(II) complex has the highest DNA intrinsic binding constant (2.20 × 105 M−1), induces extensively DNA cleavage compared to the other complexes, and exhibits the highest cytotoxicity (IC50 = 0.67 μM) against human liver cancer cell line (HepG2). Exciting, Cu(II) compound exhibits no toxicity to the nonmalignant human foetal lung fibroblast (WI‐38). Alternatively, the low cytotoxicity of the Co(II) complex correlates well with the high affinity of the compound to human serum albumin (Kb = 4.58 × 105) compared to 1.93 × 105 and 2.14 × 105 M−1 for Ni (II) and Cu (II) complexes, respectively. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of chronic evening oral administration of bromazepam alone or in combination with propranolol on ambulatory blood pressure (BP) and heart rate (HR) in mild hypertensive subjects. Methods: Thirty-seven mild hypertensive patients after a 2-week placebo period were randomized to bromazepam 3 mg, propranolol 40 mg, bromazepam 3 mg plus propranolol 40 mg or placebo for 2 weeks according to a double-blind, double dummy, cross-over design. After each treatment period, 24-h BP and HR ambulatory monitoring was performed by using a non-invasive device. Results: Ambulatory monitoring showed that during night-time SBP and DBP values were unaffected by bromazepam as compared to placebo, whereas SBP was significantly reduced by propranolol both when taken alone and in combination with bromazepam. HR nocturnal values were significantly reduced by propranolol, whereas they were significantly increased by bromazepan both when taken alone (+11.5%, p < 0.05 vs. placebo) and in combination with propranolol (+12.8%, p < 0.05 vs. propranolol). No significant difference in day-time values of SBP, DBP and HR was observed among the 4 treatment groups. Conclusions: In mild hypertensive patients, evening consumption of bromazepam for a 2-week period did not affect BP, while it increased nocturnal HR. Such an increase was observed both when bromazepam was taken alone and in combination with propranolol, which suggests that it depends on a bromazepam mediated decrease in vagal tone. Whatever the mechanism, the HR nocturnal increase might be of clinical relevance, due to the role of high HR as cardiovascular risk factor, particularly in already at risk hypertensive subjects. [ABSTRACT FROM AUTHOR]

Bromazepam is a psychoactive drug belonging to class of benzodiazepines with well-known hypnotic and sedative effects. It acts on the central neural system as an inhibitor of the neurotransmitter gamma aminobutyric acid. It is frequently prescribed for treatment of severe anxiety, to reduce tension, agitation and depression. Dissolution testing (the process by which a solid solute enters in to a solution) is a requirement for all solid oral dosage forms and is used in all phases of research and development for product release and stability testing. Tablet dissolution test is a standardized method for measuring the rate of drug release from a dosage form and it simulates the percentage of active substance that can be absorbed into the blood circulation. The direct determination of Bromazepam in pharmaceutical dosage forms using HPLC with UV detector to carry out dissolution test, have not yet been described. Development of HPLC method with UV detection for direct determination of in-vitro dissolution test of Bromazepam tablets, which can be used in the same time as method for determination of assay of Bromazepam in Bromazepam tablets, can make analytical procedure easier and quicker. A simple, selective, linear, precise and accurate RP-HPLC method has been developed and validated for assay and in-vitro dissolution test of Bromazepam tablets. The method was validated according to the guidelines set by the International Conference of Harmonization for validation of analytical procedures. The chromatographic separation was carried out using reversed phase HPLC LiChrospher RP Select B column (125 x 4.0 mm i.d.; 5μm) at temperature of 50oC. Mobile phase was consisting of the mixture of methanol, acetonitrile and potassium dihydrogen phosphate buffer (pH 7.0, adjusted with 0.5M Potassium hydroxide), with the ratio of 45:5:50 (v/v/v) and flow rate of 1.0 ml/min. The detection was carried out at 239 nm. System suitability tests were performed through evaluation of different parameters (retention time, tailing factor, retention factor and selectivity) on freshly prepared standard solution of bromazepam. The retention time of bromazepam in 0,1M HCl was 3.5 min. High percentage of recovery shows that the method is free from the interferences from excipients in test samples. Linearity of response was calculated as a ratio of peak areas of bromazepam vs. concentration in 0,1M HCl and spiked tablets in the concentration range of 0.0018 – 0.016 mgmL-1. The response was linear over the concentration range of 0.0018 – 0.016 mgmL-1 and coefficient of correlation was greater than 0.99. Good linearity shows that the proposed method may be useful for quickly and routinely determination of the percentage of dissolved bromazepam from bromazepam tablets and it can be a method of choice for assay determination in the same time. [ABSTRACT FROM AUTHOR]

Context: Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. Methods: This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. Results: From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. Conclusion: Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic. [ABSTRACT FROM AUTHOR]

The present study investigates the influence of bromazepam while executing a motor task. Specifically, we intend to analyze the changes in alpha absolute power under two experimental conditions, bromazepam and placebo. We also included analyses of theta and beta frequencies. We collected electroencephalographic data before, during, and after motor task execution. We used a Two Way ANOVA to investigate the condition (PL × Br6 mg) and moment (pre and post) variables for the following electrodes: Fp1, Fp2, F7, F3, Fz, F4, F8, C3, CZ and C4. We found a main effect for condition on the electrodes FP1, F7, F3, Fz, F4, C3 and CZ, for alpha and beta bands. For beta band we also found a main effect for condition on the electrodes Fp2, F8 and C4; for theta band we identified a main effect for condition on C3, Cz and C4 electrodes. This finding suggests that the motor task did not have any influence on the electrocortical activity in alpha, and that the existing modifications were a consequence due merely to the drug use. Despite its anxiolytic and sedative action, bromazepam did not show any significant changes when the individuals executed a finger extension motor task.

In this paper, novel univariate and multivariate regression model updating methods were developed and validated for the simultaneous determination of ternary mixture of bromazepam, diazepam and clonazepam. The univariate methods used are the mean centering of ratio spectrophotometric method and iso-absorptive point coupled with ratio-subtraction and ratio difference spectrophotometric method. Linearity, ranges, precision and accuracy of these methods were determined. The multivariate methods adopted are the principal component regression and partial least-squares. These models were estimated using nineteen mixtures as calibration set and six mixtures as validation set. The minimum root square error of predication were 0.1215 and 0.0568 for BMZ, 0.0598 and 0.0712 for DIZ and 0.0867 and 0.0753 for CNP by PLS and PCR respectively. PCR and PLS methods were successfully applied for the analysis of BMZ, DIZ and CNP in their dosage forms. Content uniformity testing of the studied pharmaceutical tablets by PLS and PCR was also determined. MCR, IPRSRD and PLS model updating enabled the determination of BMZ, DIZ and CNP in spiked human urine. Moreover, PLS model updating was applied to drug-dissolution rate testing of BMZ and DIZ in their commercial tablets. The obtained results were statistically compared with those obtained by reported methods giving a conclusion that there is no significant difference regarding accuracy and precision. [ABSTRACT FROM AUTHOR]

Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms, and drugs. Description of the dataset in three periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam, and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with three diversion profiles: (i) buprenorphine, flunitrazepam, and morphine were mentioned on overlapping secure prescription forms presented by young men; (ii) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and (iii) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion. [ABSTRACT FROM AUTHOR]

The reaction of bromazepam (7-bromo-1,3-dihydro-5-(2-pyridyl)-2 H-1,4-benzodiazepin-2-one, BZM) with Cr(III) ( 1), Fe(III) ( 2) and Ru(III) ( 3) salts gives complexes of the type [M(BZM)3]⋅3X (X = Cl or NO3). Structural characterization was extensively carried out using various analytical and spectral tools such as infrared, 1H NMR and UV-visible spectroscopies and magnetic, conductance, elemental and thermal analyses. BZM is a bidentate ligand and interacts with the metal ions via the pyridine and benzodiazepin-2-one nitrogen atoms. The magnetic and electronic properties of 2 and 3 are consistent with low-spin octahedral complexes. The three BZM molecules are non-isoenergetically coordinated to the metal ions and this is reflected in the values of the second-order interaction energy. The antibacterial activity was studied using Staphylococcus aureus and Escherichia coli. Coordination of BZM to Cr(III) or Ru(III) ions leads to a marked increase in toxicity with respect to the inactive Fe(III) complex 2. [ABSTRACT FROM AUTHOR]

The boron-doped diamond electrodes (BDDEs) with different dopant levels were applied as advanced, mercury-free and modification-free electroanalytical platforms for simple and reliable quantification of benzodiazepines, bromazepam (BZ) and alprazolam (ALZ). Cyclic voltammetric measurements revealed that the electrode reactions of both analytes were manifested by one irreversible and diffusion-controlled reduction peak at −1.10 V in Britton-Robinson buffer of pH 11 for BZ using lab-made BDDE with 1000 ppm B/C ratio and −0.84 V in BR buffer of pH 5 for ALZ using commercial BDDE with 1000 ppm B/C ratio. Differential pulse voltammetry was used for construction of calibration curves for BZ and ALZ, respectively, with the analytical parameters as follows: the linear dynamic ranges of 1 × 10 −6 –1 × 10 −4 and 8 × 10 −7 –1 × 10 −4 mol/L, the detection limit of 3.1 × 10 −7 and 6.4 × 10 −7 mol/L and the excellent repeatability with the relative standard deviation below 3% for both drugs. The developed methods were applied to analysis of the pharmaceutical tablets with the recoveries from 97.33 to 100.85% for BZ and from 94.14 to 101.32% for ALZ. The usage of BDDEs as advanced electrochemical sensors in drug analysis represents a facile and effective analytical approach which may replace mercury-based sensors and chemically modified electrodes in previous benzodiazepines sensing. [ABSTRACT FROM AUTHOR]

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 −1 , 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 −1 . Temazepam and clobazam were found in 26% (maximum concentration of 39 ng L −1 ) and 14% (maximum concentration of 11 ng L −1 ) 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 −1 . This study clearly shows that benzodiazepines are common micro-contaminants of the largest European river systems at ng L −1 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. [ABSTRACT FROM AUTHOR]

Two new photoactivatable carbon monoxide-releasing molecules (CORMs), fac-[Mn(CO)3(BZM)Br] ( 1) and [RuCl2(BZM)(CO)2] ( 2), derived from the anti-anxiety drug bromazepam (BZM) and capable of rapid release of CO upon the illumination with light-emitting diode (LED) source light (470-525 nm) have been synthesized and characterized. The photo-delivery of CO to myoglobin solution could be achieved via the illumination of 1 at 525 nm for 10 min or at 470 nm for 1 min. The addition of water to a dimethylsulfoxide (DMSO) solution of 1 increases its stability, but it decreases the rate of the CO-releasing process. CORM 2 behaves as a good visible photoCORM, whereby its two CO molecules are released within 10 min upon exposure to LED light source at 470 nm in DMSO. The illumination profile of 2 was also examined using solution . The cis/ trans stereochemistry around the Ru(II) ion was determined using quantum chemical calculations. The formation of photoCORMs leads to an improvement in the toxicity of BZM against tested microbes. [ABSTRACT FROM AUTHOR]

Rationale: Several model organisms have been employed to study the impacts of stress on biological systems. Different models of unpredictable chronic stress (UCS) have been established in rodents; however, these protocols are expensive, long-lasting, and require a large physical structure. Our group has recently reported an UCS protocol in zebrafish with several advantages compared to rodent models. We observed that UCS induced behavioral, biochemical, and molecular changes similar to those observed in depressed patients, supporting the translational relevance of the protocol. Objectives: Considering that a pharmacological assessment is lacking in this zebrafish model, our aim was to evaluate the effects of anxiolytic (bromazepam) and antidepressant drugs (fluoxetine and nortriptyline) on behavioral (novel tank test), biochemical (whole-body cortisol), and molecular parameters ( cox-2, tnf-α, il-6, and il-10 gene expression) in zebrafish subjected to UCS. Results: We replicated previous data showing that UCS induces behavioral and neuroendocrine alterations in zebrafish, and we show for the first time that anxiolytic and antidepressant drugs are able to prevent such effects. Furthermore, we extended the molecular characterization of the model, revealing that UCS increases expression of the pro-inflammatory markers cox-2 and il-6, which was also prevented by the drugs tested. Conclusions: This study reinforces the use of zebrafish as a model organism to study the behavioral and physiological effects of stress. The UCS protocol may also serve as a screening tool for evaluating new drugs that can be used to treat psychiatric disorders with stress-related etiologies. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate cortical mechanisms and to identify the areas where occur such mechanisms due to interaction between bromazepam and motor learning. The sample was composed of 45 healthy subjects randomly distributed in 3 groups: placebo (n=15), bromazepam 3 mg (n=15) or bromazepam 6 mg (n=15). To perform the experimental task, subjects sat comfortably at a distance of approximately 20 cm from the typewriter. The typewriter keyboard was covered with a wooden box to avoid visual information about the hands' position. The typewriting task was performed concomitantly with EEG recording. ANOVA two-way results indicated a decreased asymmetry in sensorimotor areas in the experimental groups. Our interpretation is that moderate doses of bromazepam may improve performance on tasks with predictable elements to promote stability of psychomotor functions, but may also impair performance on tasks executed in unpredictable environments.O objetivo do estudo foi elucidar mecanismos corticais e identificar as áreas onde estas ocorrem tais mecanismos devido à interação entre bromazepam e aprendizagem motora. A amostra compreendeu 45 sujeitos hígidos distribuídos randomicamente em 3 grupos: placebo (n=15), bromazepam 3 mg (n=15) ou bromazepam 6 mg (n=15). Para a realização da tarefa experimental, sujeitos sentaram-se confortavelmente a uma distância de aproximadamente 20 cm da máquina de escrever. O teclado da máquina foi coberto com uma caixa de madeira para evitar informações visuais sobre a posição das mãos. O registro do EEGq ocorreu simultaneamente à tarefa de datilografia. Os resultados da ANOVA two-way indicaram menor assimetria em áreas sensório-motoras nos grupos experimentais. Nossa interpretação é que doses moderadas de bromazepam podem melhorar o desempenho em tarefas previsíveis por promover estabilidade das funções psicomotoras, mas pode prejudicar o desempenho em tarefas realizadas em ambientes imprevisíveis.

The EEG has been widely employed in the assessment of electrophysiological changes induced by distinct medications. Its sensibility in detecting alterations produced by a specific substance may be enhanced by methods of quantitative analyses (qEEG). The present study aimed at investigating the modulatory effects of bromazepam on brain dynamics. The effects of bromazepam (3mg) on EEG power distribution were tested in 10 healthy individuals, in a double-blind experiment. The electrophysiological measure was analyzed across experimental conditions, moments, and electrodes, in the delta, theta, alpha and beta frequency bands separately. A significant decrease of relative power was observed in delta and theta (main effect of condition). No interactions were observed. Although the expected anxiolytic EEG profile was not observed (increased beta and decreased alpha activity), this specific result may be related to other factors such as dosage used and the subjects' general physiological state, and not necessarily to the drug itself.O EEG tem sido amplamente empregado na avaliação de mudanças eletrofisiológicas induzidas por medicações distintas.A sensibilidade desta técnica em detectar alterações produzidas por uma substância pode ser aprimorada por métodos de análise quantitativa (EEGq). O presente estudo teve por objetivo investigar os efeitos modulatórios do bromazepam na dinâmica cerebral. Os efeitos de 3mg de bromazepam na distribuição de potência cortical foram observados em 10 indivíduos sadios, em um desenho duplo-cego. A medida eletrofisiológica foi analisada nas diferentes condições experimentais, momentos e eletrodos, em delta, teta, alfa e beta separadamente. Uma diminuição significativa de potência relativa foi observada em delta e teta (efeito principal para condição). Não foram observadas interações. Embora o perfil ansiolítico do EEG (aumento de beta e diminuição de alfa) não tenha sido observado, esteresultado específico pode estar relacionado a outros fatores, tais como dose utilizada e estado fisiológico dos sujeitos, e não necessariamente à droga propriamente dita.

A significant fraction of patients are affected by persistent fear and anxiety. Currently, there are several anxiolytic drug options, however their clinical outcomes do not fully manage the symptoms. Here, we evaluated the effects of a bromazepam‑palladium derivative [2-{(7-bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-il)pyridinyl-κ2- N , N }chloropalladium(II)], [(BMZ)PdCl 2 ], on fear/anxiety and memory-related behavior in mice. For this, female Swiss mice were treated intraperitoneally (i.p.) with saline (NaCl 0.9%) or [(BMZ)PdCl 2 ] (0.5, 5.0, or 50 μg/kg). After 30 min, different tests were performed to evaluate anxiety, locomotion, and memory. We also evaluated the acute toxicity of [(BMZ)PdCl 2 ] using a cell viability assay (neutral red uptake assay), and whether the drugs mechanism of action involves the γ-aminobutyric acid type A (GABA A) receptor complex by pre-treating animals with flumazenil (1.0 mg/kg, i.p., a competitive antagonist of GABA A -binding site). Our results demonstrate that [(BMZ)PdCl 2 ] induces an anxiolytic-like phenotype in the elevated plus-maze test and that this effect can be blocked by flumazenil. Furthermore, there were no behavioral alterations induced by [(BMZ)PdCl 2 ], as evaluated in the light-dark box, open field, and step-down passive avoidance tests. In the acute toxicity assay, [(BMZ)PdCl 2 ] presented IC 50 and LD 50 values of 218 ± 60 μg/mL and 780 ± 80 mg/kg, respectively, and GSH category 4. Taken together, our results show that the anxiolytic-like effect of acute treatment with [(BMZ)PdCl 2 ] occurs through the modulation of the benzodiazepine site in the GABA A receptor complex. Moreover, we show indications that [(BMZ)PdCl 2 ] does not promote sedation and amnesia and presents the same toxicity as the bromazepam prototype. We evaluated the effects of a bromazepam-palladium complex on fear, anxiety and memory-related behaviors in mice. The results showed that the anxiolytic-like occurs through modulation of the benzodiazepine site in the GABA A receptor complex. There are indications that the complex does not promote sedation, amnesia and toxicity higher than bromazepam. [Display omitted] • Palladium-bromazepam complex, [(BMZ)PdCl 2 ]. • [(BMZ)PdCl 2 ] showed an anxiolytic-like effect. • [(BMZ)PdCl 2 ] did not affect locomotor activity and memory. • [(BMZ)PdCl 2 ] showed similar acute toxicity to bromazepam. [ABSTRACT FROM AUTHOR]

The early stages of visual information processing, involving the detection and perception of simple visual stimuli, have been demonstrated to be sensitive to psychotropic agents. The present study investigated the effects of an acute dose of bromazepam (3 mg), compared with placebo, on the P100 component of the visual evoked potential and reaction time. The sample, consisting of 14 healthy subjects (6 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs the initial stage of visual information processing, as observed by an increase in P100 latency.Os estágios iniciais do processamento da informação visual, envolvendo a percepção e detecção de um estímulo visual simples, tem demonstrado serem sensíveis a agentes psicotrópicos. O presente estudo investigou os efeitos de uma dose aguda de bromazepam (3 mg), comparado com placebo, no componente P100 do potencial evocado visual e no tempo de reação. A mostra consistiu de 14 sujeitos sadios (6 homens e 8 mulheres), submetidos a uma tarefa de discriminação visual, a qual empregou o paradigma "oddball". Os resultados sugerem que o bromazepam (3 mg) prejudica o estágio inicial do processamento da informação visual, como observado pelo aumento da latência do P100.

Benzodiazepines are among the most commonly prescribed medications due to their therapeutic efficacy in reducing anxiety and inducing sleep. Consequently, they have been widely employed in the pharmacological treatment of several disorders. Nevertheless, few studies have analyzed the effects of bromazepam in electroencephalographic activity (EEG). The present study aimed at investigating the modulatory effects of this drug on brain dynamics. Specifically, the effects of bromazepam (3mg) on EEG coherence were tested in a double-blind experiment. The sample, consisting of 10 healthy subjects (5 male and 5 female), was submitted to ten minutes of EEG recording. The electrophysiological measure (coherence) was analyzed across three experimental conditions: bromazepam, placebo 1, and placebo 2. Results indicate that bromazepam significantly increases cortical interhemispheric coherence.Benzodiazepínicos estão entre as medicações mais comumente prescritas devido à sua eficácia terapêutica para reduzir ansiedade e induzir sono. Conseqüentemente, eles têm sido amplamente empregados no tratamento de diversas desordens. No entanto, poucos estudos têm analisado os efeitos do bromazepam na atividade eletrencefalográfica (EEG). Assim, o presente estudo teve por objetivo investigar os efeitos modulatórios desta droga na dinâmica cerebral. Especificamente, os efeitos de 3 mg de bromazepam na coerência eletrocortical foram analisados em um experimento duplo-cego. A amostra consistiu de 10 sujeitos sadios (5 homens e 5 mulheres), submetidos a dez minutos de captação do sinal de EEG. A medida eletrofisiológica (coerência) foi analisada em três condições experimentais: bromazepam, placebo 1 e placebo 2. Os resultados sugerem que o bromazepam aumenta significativamente a coerência cortical inter-hemisférica.

Background/Aim. Benzodiazepines are among the most frequently ingested drugs in self-poisonings. Elderly may be at greater risk compared with younger individuals due to impaired metabolism and increased sensitivity to benzodiazepines. The aim of this study was to assess toxicity of benzodiazepines in elderly attempted suicide. Methods. A retrospective study of consecutive presentations to hospital after self-poisoning with benzodiazepines was done. Collected data consisted of patient's characteristics (age, gender), benzodiazepine ingested with its blood concentrations at admission, clinical findings including vital signs and Glasgow coma score, routine blood chemistry, complications of poisoning, details of management, length of hospital stay and outcome. According the age, patients are classified as young (15-40-year old), middle aged (41-65-year old) and elderly (older than 65). Results. During a 2-year observational period 387 patients were admitted because of pure benzodiazepine poisoning. The most frequently ingested drug was bromazepam, the second was diazepam. The incidence of coma was significantly higher, and the length of hospital stay significantly longer in elderly. Respiratory failure and aspiration pneumonia occurred more frequently in old age. Also, flumazenil was more frequently required in the group of elderly patients. Conclusion. Massive benzodiazepines overdose in elderly may be associated with a significant morbidity, including deep coma with aspiration pneumonia, respiratory failure, and even death. Flumazenil is indicated more often to reduce CNS depression and prevent complications of prolonged unconsciousness, but supportive treatment and proper airway management of comatose patients is the mainstay of the treatment of acute benzodiazepine poisoning. [ABSTRACT FROM AUTHOR]

Background The majority of infertile women are young and healthy but exhibit stress, anxiety, and other psychological disorders associated with infertility. This anxiety should be attenuated with appropriate drugs during premedication. Moreover, after the procedure, patients report visceral pain resulting from cervical manipulation, which should be relieved with appropriate analgesia. Objectives The aim of this study was to evaluate and compare the clinical efficacy of oral premedication with pregabalin and bromazepam for sedation in terms of effectiveness and postoperative analgesia in patients undergoing embryo transfer during in-vitro fertilization (IVF). Patients and methods A total of 60 healthy infertile consented female patients younger than 39 years with ASA physical status I or II who were scheduled for embryo transfer during IVF were randomized to receive either pregabalin (300 mg) (group A), bromazepam (3 mg) (group B), or placebo (folic acid 0.5 mg) (group C) 90 min before surgery as oral premedication. The Ramsay sedation scale was used to evaluate preoperative sedation. Hemodynamic data were recorded before premedication, just after induction, after recovery, and 2 and 4 h postoperatively. Severity of postoperative pain was assessed using a visual analogue scale ( VAS). Results Perioperative sedation levels were lighter in the pregabalin group than in the bromazepam group, as there were statistically significant differences in terms of attenuation in mean arterial blood pressure and heart rate. Moreover, VAS score was significantly lower in the pregabalin group at induction, recovery, and 2 and 4 h after surgery. Conclusion This study showed that the use of pregabalin 300 mg or bromazepam 3 mg causes good preoperative sedation with hemodynamic stability intraoperatively together with decreasing postoperative pain in embryo transfer during IVF procedure. [ABSTRACT FROM AUTHOR]

Os efeitos sedativos do bromazepam no desempenho cognitivo têm sido amplamente investigados. Várias abordagens têm sido implementadas no intuito de avaliar a influência do bromazepam em sujeitos submetidos à tarefa motora. Neste contexto, o presente estudo objetiva avaliar as alterações eletrofisiológicas em sujeitos expostos à tarefa de datilografia e tratados com bromazepam (6 mg). Os dados do EEGq foram gravados simultaneamente à tarefa. Em particular, a potência relativa na banda delta (0,5-3,5 Hz) foi analizada. O tempo de execução e erros durante a tarefa foram considerados variáveis comportamentais. O grupo experimental (bromazepam 6 mg) demonstrou melhor desempenho e valores de potência relativa mais elevados que o grupo controle (placebo). Estes resultados sugerem que menor nível de ansiedade favorece o desempenho motor.