Search Results (84)

Sleep disorders, such as insomnia and narcolepsy, significantly impact quality of life. They are often associated with long-term health consequences, including cardiovascular disease, immune dysfunction, and cognitive impairment. While traditional treatments, such as sedatives and hypnotics, can be effective, they are limited by issues of tolerance and dependence. The orexinergic system, particularly the orexin 1 receptor (OXR1), has emerged as a promising therapeutic target due to its central role in regulating sleep–wake cycles. In this study, we investigate the molecular interactions of three OXR1 antagonists—daridorexant, lemborexant, and suvorexant—using an integrated computational approach combining molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and the molecular fractionation with conjugate caps (MFCC) methodology. The MFCC approach enabled the precise quantification of interaction energies between ligands and key receptor residues, providing detailed insights into the contributions of specific amino acids to binding stability. Our results reveal that residues such as GLU204, HIS216, and ASN318 play critical roles in stabilizing ligand–receptor interactions, with a marked decrease in binding energy magnitude as dielectric constants increase. Daridorexant exhibited the strongest interaction energy, driven by hydrogen bonds and hydrophobic contacts, while lemborexant and suvorexant showed distinct stabilization patterns mediated by hydrophobic interactions. These findings provide a robust molecular basis for the rational design of next-generation OXR1 antagonists with improved efficacy and safety profiles. By elucidating drug–receptor interactions at the atomic level, this research underscores the impact of integrated computational approaches in drug discovery. It supports the development of precise targeted therapies for sleep disorders. Full article

Benzodiazepines (BZDs), potent sedative and hypnotic drugs widely prescribed in psychiatry, pose a high risk of dependence and are globally abused. This study used wastewater-based epidemiology to investigate the consumption patterns of BZDs across four wastewater treatment plants (WWTPs) in Wuhu, China. A total of 16 BZDs and three metabolites were detected in influents and effluents, with concentrations reaching up to 90 ng/L (quetiapine fumarate) and 18.4 ng/L (diazepam). Most BZDs had a poor removal efficiency except quetiapine fumarate (>98% removal). The consumptions of BZDs in WWTPs ranged from <0.02 (lormetazepam) to 2700 mg/day/1000 people (quetiapine fumarate). Seasonal variation was found in BZD usage, where the consumptions in winter and spring were significantly higher than those in summer and autumn. It was worth noting that nimetazepam may be abused during the sampling campaign. Urban areas with higher housing prices match higher BZD consumption, correlating with greater stress and insomnia rates. This study reveals the relationship between socioeconomic factors and BZD consumption patterns, provide a new path to addressing community public health. Full article

The benzodiazepines are essential drugs used in medicine for anxiolytic, sedative, and hypnotic effects. According to the World Health Organization, the benzodiazepines are the most prescribed hypnotic drugs in the last decade (2010 at time), and their inappropriate use can damage the environment and human health. The availability of efficient analytical methods is crucial for the determination of these drugs in a complex matrix such as biological samples in clinical settings. In the last decade, several methods have been developed and have been applied to the detection and determination of benzodiazepines or their derivates. The present manuscript reviews selective and sensitive methodologies based on chromatographic, electrophoretic, and electrochemical systems for the determination of benzodiazepines in biological samples, covering the time of the last years and providing detailed information on sample pretreatment and instrumental conditions. Full article

Background/Objectives: The association between vestibular symptoms and psychological distress has been previously studied, mainly with the use of questionnaires. The purpose of this study is to compare the consumption of psychotropic drugs between a group of patients with vertigo and a control group. Methods: A prospective cross-sectional, observational, case–control study was carried out, including 506 patients (232 with Ménière’s disease, 79 with vestibular migraine, 34 with vestibular neuritis, and 161 with benign paroxysmal positional vertigo). In total, 253 participants were included in the control group. Both groups were comparable regarding age, sex, and history of previous psychiatric diseases. Results: The percentage of patients with vertigo who consumed psychotropic drugs (41.3%) was higher than the percentage of the control group who did so (26.9%) (Fisher’s exact test, p < 0.0001; OR = 1.914, CI95% (1.377; 2.662)). The mean number of psychotropic drugs consumed was also higher (Mann–Whitney test, p = 0.0003) in cases (0.68 ± 0.959) than in controls (0.47 ± 0.889). This higher consumption in the group of patients with vertigo was found for all pharmacological groups studied, being especially relevant regarding “anxiolytics and hypnotics and sedatives” and “antidepressants”. No statistically significant differences in the consumption of psychotropic drugs between types of vestibular disorders were observed. The longer the symptoms were present, the higher the prevalence of psychotropic drug use was observed. Conclusions: A relationship between vertigo and consumption of psychotropic drugs was found. Recording the consumption of these drugs is proposed as an objective method to better understand the psychological distress that patients with vertigo may suffer from. Full article

Valerian possesses a multitude of pharmacological effects, including sedative and hypnotic properties, antihypertensive effects, antibacterial activity, and liver protection. Insomnia, one of the most prevalent disorders in contemporary society, significantly impacts people’s daily lives. This study aims to explore the anti-insomnia effects of valerian volatile oil (VVO) and investigate its potential mechanism of action through chemical analysis, network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation. Through gas chromatography–mass spectrometry (GC-MS) analysis and drug-likeness screening, we identified 38 active compounds. Network pharmacology studies revealed that these 38 compounds might affect 103 targets associated with insomnia, such as monoamine oxidase B (MAOB), dopamine receptor D2 (DRD2), monoamine oxidase A (MAOA), interleukin 1β (IL1B), solute carrier family 6 member 4 (SLC6A4), prostaglandin-endoperoxide synthase 2 (PTGS2), and 5-hydroxytryptamine receptor 2A (HTR2A), which contribute to regulating the neuroactive ligand–receptor interaction, 5-hydroxytryptaminergic synapse, and calcium signaling pathways. The results of the molecular dynamics simulations indicated that bis[(6,6-dimethyl-3-bicyclo[3.1.1]hept-2-enyl)methyl] (E)-but-2-enedioate exhibited a stabilizing interaction with MAOB. The animal studies demonstrated that gavage administration of a high dose (100 mg/kg) of VVO significantly diminished autonomous activity, decreased sleep latency, and extended sleep duration in mice. Furthermore, the results of the Western blot experiment indicated that VVO interacts with MAOB, resulting in decreased expression levels of MAOB in the cerebral cortex. This study demonstrates the protective mechanism of VVO against insomnia through chemical analysis, network pharmacology, and experimental validation and extends the possible applications of VVO, which is a potential therapeutic ingredient for use in insomnia treatment. Full article

Background/Objectives: Approximately one in five individuals will experience major depressive disorder (MDD), and 30% exhibit resistance to standard antidepressant treatments, resulting in a diagnosis of treatment-resistant depression (TRD). Historically, opium was used effectively to treat depression; however, when other medications were introduced, its use was discontinued due to addiction and other hazards. Recently, kappa opioid receptor (KOR) antagonism has been proposed as a potential mechanism for treating TRD. The main research question is whether commonly used psychotropic medications possess KOR antagonist properties and whether this characteristic could contribute to their efficacy in TRD. Methods: We investigated the antinociceptive effects of many psychotropic medications and their interactions with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of these agents. Results: The antidepressants mianserin and mirtazapine (separately) induced dose-dependent antinociception, each yielding a biphasic dose–response curve. Similarly, the antidepressant venlafaxine produced a potent effect and reboxetine produced a weak effect. The antipsychotics risperidone and amisulpride exhibited a dose-dependent antinociceptive effect. The sedative–hypnotic zolpidem induced a weak bi-phasic dose-dependent antinociceptive effect. All seven psychotropic medications elicited antinociception, which was reversed by the non-selective opiate antagonist naloxone and, separately, by the kappa-selective antagonist Nor-BNI. Conclusions: Clinical studies are mandatory to establish the potential efficacy of augmentation of the treatment with antidepressants with these drugs in persons with treatment-resistant depression and the optimal dosage of medications prescribed. We suggest a possible beneficial effect of antidepressants with kappa antagonistic properties. Full article

Niaprazine is a sedative-hypnotic drug initially developed as an antihistamine and used for its notable sedative effects, particularly in children. Following its withdrawal from the market by the producer, the drug has been administered as magistral formulations available in syrup form, but there are several important disadvantages to this, including instability, taste issues, lack of controlled release, and the potential for unreliable dosing due to incomplete swallowing. There is also an increased risk of dental caries, as well as the fact that these formulations are not suitable for children who suffer from diabetes. The purpose of the current investigation is to prepare and characterize xanthan gum-based gels for the oral administration of niaprazine. Niaprazine gels appear as transparent-whiteish, non-sticky substances, with the drug uniformly dispersed throughout the systems. They are also stable over time. Dynamic rheology revealed their advantageous shear-thinning properties, which enable the formulation to be flexibly dosed orally through administration via syringe. During experimentation, the evaluation of the mucoadhesion features and the in vitro drug release profile were also performed. The results demonstrate that the formulation may represent an alternative to niaprazine syrup, allowing easy preparation, administration, and increased compliance in various categories of patients, including pediatric. Full article

Background: The effects of anesthetic drugs on myocardial cells have been a subject of research for the last 50 years. The clinical benefits of halogenated agents, particularly sevoflurane, have been demonstrated in cardiac surgery patients. These benefits are due to the action of different enzymes and a variety of molecular pathways mediated by the action of small noncoding RNAs (sRNA) such as microRNAs (miRNAs). However, the modulation potential induced by anesthetic drugs on the miRNA expression and their cardioprotective effects is unknown. Objective: To analyze the variation in the expression of a panel of miRNAs induced by halogenated agents to identify their cardioprotective effects. Aims: Variations in the expression of specific miRNAs induce the potential cardioprotective effects of halogenated agents. Methods: An ischemia/reperfusion (I/R) in vitro model of primary human cardiac myocytes (HCMs) was performed. Four study groups were performed: control group (standard culture conditions), I/R group (without hypnotic drugs exposition), I/R-propofol group (I/R-P), and I/R-sevoflurane group (I/R-S). The secretion of p53 and Akt1 cytokines was quantified in the different cell study groups using an Enzyme-Linked ImmunoSorbent Assay, and the differentially expressed miRNAs were identified carrying out a complete genomic sequencing using the Next Generation Sequencing (NGS). Results: HCMs subjected to the I/R procedure and exposed to sevoflurane showed lower secretion levels of p53 factor and higher levels of Akt-1 cytokine compared to HCMs exposed to propofol (p53: I/R-S: 10.43 ± 0.91 ng/mL; I/R-P: 137.92 ± 7.53 ng/mL; p > 0.05); (Akt1: I/R-S: 0.62 ± 0.12 ng/mL; I/R-P: 0.23 ± 0.05 ng/mL; p > 0.05). The miRNA gene expression analysis (NGS) showed significantly increased expression of the hsa-miR-140-5p and hsa-miR-455-5p, both miRNAs associated with cardiac function; the hsa-miR-98-5p and hsa-miR-193a-5p, both related to apoptosis inhibition; and the hsa-let-7d-5p associated with myocardial protection. This increase was observed in the HCMs group exposed to sevoflurane in comparison to the propofol group. Conclusions: Sevoflurane-induced miRNAs overexpression confers cardioprotection through various mechanisms at the DNA level and the different signaling pathways levels, such as Akt/ERK. Full article

Background/Objectives: The prevalence of mental health disorders has been rising in Saudi Arabia, which may have been exacerbated by the COVID-19 pandemic. Therefore, the aim of our study was to examine the usage patterns of various psychotropic drugs before and during the pandemic. Methods: This cross-sectional study was conducted at the psychiatric outpatient clinic of a single hospital in Saudi Arabia from 1 October 2018 to 31 March 2023. Electronic medical records were used to gather information on all adult patients who were prescribed at least one antidepressant, antipsychotic, or anxiolytic/sedative/hypnotic medication. The data were analyzed using descriptive statistics and multivariable logistic regression model. Results: In the 4846 participants in the study, the total frequently prescribed psychotropics during the pandemic were antidepressants (2119 prescriptions), then antipsychotics (1509 prescriptions), and anxiolytics/sedatives/hypnotics (780 prescriptions). The mean before and during the pandemic for olanzapine was (41.86 vs. 23.55) and risperidone was (39.00 vs. 22.18), indicating a significant difference for both medications (p = 0.0003). Psychotropic drug use during the COVID-19 pandemic was significantly higher among the female patients (OR = 1.15, 95% CI [1.06–1.26]) and those aged 18–39 years (OR = 1.65, 95% CI [1.52–1.80]). Antidepressant and antipsychotic use were significantly lower than anxiolytic/sedative/hypnotic use during the pandemic (OR = 0.74, 95% CI [0.65–0.84]; OR = 0.66, 95% CI [0.58–0.75], respectively). Conclusions: The prescription rate of anxiolytics/sedatives/hypnotics was higher than that of antidepressants and antipsychotics. Furthermore, women and individuals aged ≤40 years were at a higher risk of psychotropic medication use. To mitigate stress, anxiety, and depression in Saudi Arabia, policymakers should implement mental health screening initiatives. Full article

Mental health is an important segment in preserving overall health and represents a significant public health issue. In modern times, mental health disorders have risen, often requiring complex pharmacotherapy and chronic monitoring. The aim of this research was to determine the prevalence and clinical significance of potential psychotropic drug interactions in outpatient settings and compare the differences in potential drug–drug interaction (pDDIs) exposure with age. The psychotropic drugs included antipsychotics—N05A, anxiolytics—N05B, hypnotics and sedatives—N05C, and antidepressants—N06A. This retrospective study analyzed prescribed pharmacotherapy in 492 outpatients who were treated with at least one psychotropic drug. We determined 1.64 prescribed psychotropic drugs per patient and 2.2 pDDIs that involved psychotropic drugs. In total, 2285 pDDIs were recorded, of which almost half (47.6%) were pDDIs with psychotropic drugs. More prescribed psychotropic drugs were found in patients younger than 65 years, and equal exposure to pDDIs of psychotropic drugs (p = 0.5077) was found in both age groups. The most commonly identified psychotropics involved in pDDIs were benzodiazepines, promazine, and zolpidem. The results indicate that psychotropic drug interactions represent important drug-related problems for primary health care. The widespread use of psychotropic drugs and the determined clinical significance of their interactions require pharmacist interventions which can reduce the prevalence of pDDIs and increase patient safety. Full article

This study proposes a portable and IoT-based electrochemical point-of-care sensing device for detecting zopiclone in cocktails. The system utilizes an electrochemical laccase biosensor and a potentiostat, offering a low-cost and portable device for detecting this sedative drug in cocktails. The sensor characterization experiments demonstrated the linear behavior of the oxidation and reduction currents for each of the targeted concentrations of zopiclone, enabling their detection and quantification even when mixed with an interfering substance. The proposed system could be used for the in situ analysis of cocktails, providing a valuable tool for monitoring the presence of hypnotic drugs in various social and clinical settings. The study utilized materials and reagents, including zopiclone, lab-made lemon juice, lab-made tequila, and lab-made triple sec, all prepared with reactants obtained in Bogotá, Colombia. The potentiostat used in the system was designed to manage cyclic voltammetry measurements. The electrochemical cells’ durability and longevity were also tested and characterized, with all electrodes undergoing 200 tests and their performance degradation varying according to the molecule used. The study concludes that the proposed system offers a valuable tool for detecting and monitoring pharmaceutical substances in various interfering ingredients that build up cocktails. Further research and application of this system can help address the global concern surrounding the administration of hypnotic substances to unknowing consumers through food or drinks to enable robbery and sexual assault. Full article

Coumarin and its annulated heterocycles are mainly found in natural products, many of which show significant biological activities and are used extensively for the preparation of pharmaceutical products. Investigation revealed that many heterocyclic compounds fused with coumarin moiety exhibited antihelmentic, hypnotic, insecticidal, antifungal, and anti-coagulant properties. In industry, coumarin scaffolds are widely used for the preparation of drugs, agrochemicals, pesticides, and dyes. In recent studies, several coumarin derivatives have been used in materials science for the preparation of organic cell imaging materials, fluorescent biological probes, etc. Due to their immense application potential in biological science and material chemistry, much attention has been paid by researchers towards the synthesis of a new class of coumarin annulated heterocycles. In this paper, the synthesis of coumarin-annulated polycyclic heterocycles via sequential Claisen rearrangement and tin-hydride mediated radical cyclization is reported. The requisite starting materials 3-((4-chlorobut-2-yn-1-yl)oxy)-2H-chromen-2-one (1) was prepared from 3-hydroxycoumarin and 1,4-dichlorobut-2-yne. The Claisen rearrangement of 1 in refluxing chlorobenzene afforded 1-(chloromethyl)pyrano[2,3-c]chromen-5(3H)-one (2). Finally, radical cyclization reactions were carried out smoothly using ⁿBu₃SnH and AIBN in toluene at 110 °C, leading to the coumarin-annulated polycyclic heterocycles in high yields. The process is operationally simple and easy to work-up, making it convenient for the preparation of coumarin annulated heterocycles. Full article

Purpose: To assess (I) whether, in autopsy-proven lethal intoxications with opiates/opioids, a dilatation of the common bile duct (CBD) is still visible in postmortem computed tomography (PMCT) and (II) if a dilatation of the CBD might also be measurable for other substance groups (e.g., stimulants, hypnotics, antipsychotics, etc.). Methods: We retrospectively measured the CBD using PMCT in cases with lethal intoxication (n = 125) and as a control group in cases with a negative toxicological analysis (n = 88). Intoxicating substances were classified into the subgroups (opiates, opioids, stimulants, hypnotics, antipsychotics, gasses, and others). Significance between the study and control groups was tested with the Mann–Whitney U test, and correlations were examined by using crosstables. Results: There was a statistically significant difference between the CBD diameters in the intoxication group overall, when compared to the CBD diameter in the control group (p < 0.001). For both subgroups of “opiates” and “opioids”, there was a strong statistically significant difference between the CBD diameter (being wider) in those groups compared to the control group (both p = 0.001). For the three subgroups “hypnotics”, “stimulants”, and “psychotropic drugs”, there was no statistically significant difference between the CBD diameters in the intoxication subgroups when compared with the control group. The other subgroups were too small for statistical analysis. Conclusion: A dilated common bile duct in postmortem computed tomography might be used as an indication for a lethal opioid or opiate intoxication only in regard to the specific case circumstances or together with other indicative findings in a postmortem investigation. Full article

Background/Objectives: Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and mental health issues. It affects approximately 1.78% of the general population; an estimated 4:1 ratio between women and men is observed. It significantly impacts quality of life and carries both clinical and social stigma. This study aims to evaluate the relationship between drug use and mental health in female patients with fibromyalgia. Methods: This study is prospective, observational, and cross-sectional. A questionnaire was administered to 544 subjects, achieving a representative sample size from a population of 800,000 subjects by using an algorithm for proportion estimation with a known sampling frame. The selection was non-random, making the sampling non-probabilistic. Logistic regression models were applied to assess the effect of drug use on perception of mental health; presence of symptoms such as comprehension and memory problems, insomnia, depression, and anxiety; and severity of cognitive symptoms and non-restorative sleep. To quantify the impact, odds ratios and confidence intervals have been observed. Results: The findings indicate the non-recommended use of medications and reveal the ineffectiveness and adverse effects of drug interactions on mental health. The use of benzodiazepines and sedative-hypnotics is significantly associated with a negative perception of mental health. Benzodiazepines do not improve symptoms or significantly reduce their severity. SSRI antidepressants do not enhance mental health perception; however, when used exclusively, they are effective in reducing the severity, but not the prevalence, of cognitive symptoms. Conclusions: The results highlight the complexity of pharmacological management in FM and raise concerns about the inappropriate use of ineffective or counterproductive drug interactions affecting patients’ mental health. They underscore the need for multidisciplinary and personalized strategies that include close and careful monitoring, as well as the simultaneous use of non-pharmacological treatments that have demonstrated evidence in improving quality of life without negatively affecting mental health, such as patient education, psychological therapy, physiotherapy, and mindfulness. Full article

Barbituric acid is a heterocyclic compound with various pharmacological and biological applications. This review paper provides a comprehensive overview of barbituric acid’s synthesis, reactions, and bio-applications, highlighting its multifaceted role in various fields. Many heterocyclic derivatives were formed based on barbituric acid, for instance, pyrano-fused pyrimidine derivatives, spiro-oxindole derivatives, chrome-based barbituric acid derivatives, and many more via the atom economic method, Michael addition reaction, Knoevenagel condensation reaction, etc. In the context of bio-applications, this review examines the production of a wide range of bioactive drugs like anti-histamine, anti-leprotic, sedative–hypnotic, anti-inflammatory, anti-urease, antiviral, anti-AIDS, antimicrobial, antioxidant, anticonvulsant, anesthetic agent, antitumor, and anticancer drugs using efficient multicomponent reactions. By showcasing the versatility and potential of this compound, it aims to inspire further research and innovation in the field, leading to the development of novel barbituric acid derivatives with enhanced properties and diverse applications, with coverage of the literature relevant up to 2024. Full article