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The use of medicinal plants as an alternative phytotherapeutic remedy against mild illnesses and dysfunctions is increasingly embraced by people. Among these dysfunctions, episodes of nervousness and anxiety due to lack of sleep and insomnia are becoming more and more frequent among the population. To remedy these problems, several plants with sedative activity are recommended. In particular, valerian root (Valeriana officinalis L.) is the most recommended and studied with a significant difference. This study presented a quantification of the phytomelatonin contents in valerian root and several related and recommended herb supplements against nervousness, anxiety, and insomnia. The results showed the presence of phytomelatonin in all the samples analyzed. The high phytomelatonin contents in valerian root and its supplements indicated that, in addition to the known constituents of valerian root such as valerenic acid, phytomelatonin also contributed to the phytotherapeutic activity of this plant since the relaxing and sleep-inducing activity of melatonin is well documented. The recommended daily doses of valerian are analyzed according to their phytomelatonin content, and recommendations are given on the possible synergistic action of the components of valerian as a relaxant and sleep inducer in patients with these dysfunctions. It is also recommended to document the phytomelatonin contents in phytotherapeutic preparations. [ABSTRACT FROM AUTHOR]

GC–MS and HPLC analyses of the hydromethanolic extracts of the truffles Tirmania nivea (TN) and Tirmania pinoyi (TP) revealed the presence of 18 metabolites and 11 polyphenols, respectively. In vivo, TP extract protected against subcutaneous pentylenetetrazole (scPTZ) and maximal electric shock (MES)‐induced convulsions faster than TN extract. TP extract (100 and 300 mg/kg) showed 100% protection and longer duration than TN extract in the scPTZ test. Similarly, at 300 mg/kg, TP demonstrated a quicker start (75%) and longer duration of action (100%) than TN in MES test. In the scPTZ test, ED50 of TP demonstrated greater anticonvulsant efficacy than that of TN. In mice given TP and TN treatments, the brain GABA levels noticeably increased. TP (100 and 300 mg/kg) produced a notable sedative effect in open‐field test, whereas TN (100 or 300 mg/kg) and TP (300 mg/kg) reduced sleep latency by 52%, 45%, and 79%, respectively. In writhing test, TN (100 or 300 mg/kg) significantly enhanced analgesic efficacy by 50 and 87%, respectively. Comparatively, in formalin test, TP and TN at a dosage of 300 mg/kg decreased the length of the licking by 34 and 59%, respectively. For the first time, this study explains the anticonvulsant, sedative, central, and peripheral analgesic activities of truffle extracts. [ABSTRACT FROM AUTHOR]

Abstract Background This Bayesian network analysis was performed to assess the effects of different intravenous sedatives on outcomes in adult critically ill patients. Methods We searched for and gathered data from MEDLINE, Cochrane Central Register of Controlled Trials, Elsevier and Web of Science databases. Bayesian network analysis was performed to evaluate the effect of different intravenous sedatives on outcome in adult critically ill patients. Random errors were evaluated by trial sequential analysis (TSA). Results Twenty-seven studies including 8,599 critically ill adult patients were enrolled in the analysis. Comparisons among lorazepam, midazolam, propofol, dexmedetomidine, haloperidol and placebo or usual care were presented in a network plot. No significant differences were found for longest mortality in critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. Meanwhile, midazolam had a longer ICU length of stay when compared with placebo, propofol and usual care. Subgroup analyses were performed respectively in sepsis, invasive ventilated patients and postoperative patients, as well as patients with higher severity of disease. Lower mortality was found in dexmedetomidine group when compared with placebo in postoperative patients. No differences were found for mortality, ICU length of stay and incidence of delirium in other subgroups. When compared with other sedatives, dexmedetomidine shortened ICU length of stay significantly in ventilated patients. TSA indicated lack of firm evidence for a beneficial effect. Conclusions No differences were found for longest mortality of different sedatives in adult critically ill patients. However, when compared with midazolam, dexmedetomidine had a shorter ICU length of stay and a lower incidence of delirium. TSA indicated lack of firm evidence for the results. More powered, randomized, controlled trials are needed to determine the effects.

The use of medicinal plants as an alternative phytotherapeutic remedy against mild illnesses and dysfunctions is increasingly embraced by people. Among these dysfunctions, episodes of nervousness and anxiety due to lack of sleep and insomnia are becoming more and more frequent among the population. To remedy these problems, several plants with sedative activity are recommended. In particular, valerian root (Valeriana officinalis L.) is the most recommended and studied with a significant difference. This study presented a quantification of the phytomelatonin contents in valerian root and several related and recommended herb supplements against nervousness, anxiety, and insomnia. The results showed the presence of phytomelatonin in all the samples analyzed. The high phytomelatonin contents in valerian root and its supplements indicated that, in addition to the known constituents of valerian root such as valerenic acid, phytomelatonin also contributed to the phytotherapeutic activity of this plant since the relaxing and sleep-inducing activity of melatonin is well documented. The recommended daily doses of valerian are analyzed according to their phytomelatonin content, and recommendations are given on the possible synergistic action of the components of valerian as a relaxant and sleep inducer in patients with these dysfunctions. It is also recommended to document the phytomelatonin contents in phytotherapeutic preparations.

Polygoni Multiflori Caulis (PMC) has been traditionally served as a functional medicine due to its various biological activities, but a lack of researches focused on the sleep-enhancing effects of flavonoids from PMC. In this study, the total flavonoids (PMCF) were isolated from PMC. In vitro antioxidant experiments suggested that PMCF exhibited remarkable antioxidant capacity, as evidenced by its scavenging activity on several radicals and reducing power. Subsequently, PMCF was given to insomnia mice via intragastric administration. In behavior test, PMCF exhibited sleep-enhancing effect through suppressing depression, shortening the sleep latency time while prolonging the duration sleep time in insomnia mice. To clarified the mechanism, the neurotransmitter receptors, cytokines and hormone in brain were investigated. PMCF exhibited significant sleep promoting effect by up-regulating the expression levels of hormone-related genes, and producing stimulation on the immune system by increasing interleukin-1β mRNA expression. In addition, PMCF-mediated sleep promotion accompanied the recovery of 5-hydroxytryptamine 1 A (5-HT 1A), γ-aminobutyric acid A receptor α2 (GABA A Rα2) and GABA A receptor α3 (GABA A Rα3) mRNA expression, which was more effective in the hypothalamus. Collectively, all these data implied that PMCF might produce beneficial activities in relieving sleep disturbances via the antioxidant pathway, as well as the immune, serotonergic and GABAergic systems. • Flavonoids (PMCF) and its main constituents were isolated from Polygoni Multiflori Caulis. • PMCF exhibited remarkable antioxidant capacity in in vitro experiments. • PMCF could modulate the sleep behavior to promote sleep in insomnia mice. • PMCF reversed PCPA-mediated suppression of PGD 2 , DPR and IL-1β mRNA expressions. • PMCF regulated multi-targets in 5-HT and GABAergic neurons to achieve sleep–promoting. [ABSTRACT FROM AUTHOR]

Mental and neurological disorders are conditions that affect thoughts, emotions, behavior, and relationships. Malpighia mexicana A. Juss. is a plant used in Mexican traditional medicine for the treatment of such disorders. This work aimed to investigate the antidepressant, anxiolytic, sedative, hypnotic, and anticonvulsant effects of the acetonic extract (MmAE) of M. mexicana and its fractions (F3, F4-10, F14) using the forced swimming test (FST), elevated plus maze (EPM), open field test (OFT), pentobarbital-induced sleep test (PBTt), and pentylenetetrazol-induced seizure test (PTZt). MmAE, F3, F4-10, F14, and vehicle were administrated orally 24, 18, and 1 h prior to the evaluations. Imipramine (15 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the FST, while diazepam (1 mg/kg, p.o.) was administrated 1 h prior to the evaluations as a positive control for the EPM, OFT, PBTt, and PTZt. MmAE had an anxiolytic effect; MmAE and F3, F4-10, and F14 showed an antidepressant effect, sedative effect, hypnotic effect, and anticonvulsant effect. Using HPLC, we identified the compounds quercetin 3-O-rutinoside (1), kaempferol 3-O-glucoside (2), luteolin 7-O-glucoside (3), quercetin (4), and kaempferol (5) in MmAE and compounds (1), (2), and (3) in F14. Using GC-MS, we identified α-tocopherol, phytol, and β-amyrin in F3; β-tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10; and α- tocopherol, phytol, β-sitosterol, and β-amyrin in F4-10. The neuropharmacological effects found in this work may be due to the presence of vitamins, phytosterols, terpenes, and flavonoids. This research requires further study to clarify the mechanisms of action of the identified compounds.

Ganoderma lucidum is known as lingzhi mushroom, which is said to have medicinal properties by the local residents. This research was focused to assess the antidepressant, anxiolytic, and sedative activities of the mentioned mushroom extracts by means of in vivo and in silico approaches. The antidepressant, anxiolytic, and sedative properties of the methanol extracts of G. lucidum (MEGL) were assessed using the forced swim test hole board, open field test, elevated plus maze, hole cross test, and thiopental sodium-induced sleeping time. The extracts revealed significant antidepressant, anxiolytic, and sedative activities in a dose-dependent manner. Rutin and quercetin were found to be the most effective enzyme inhibitors in the molecular docking study. According to the findings of in vivo and molecular docking study, it could be forecast that, the extract could have substantial antidepressant, anxiolytic, and sedative characteristics and deep molecular strategies on this extracts might create a target for the development of novel therapeutics. Further investigations are needed to appraise the molecular mechanisms implicated and isolate the bioactive components.

Objective: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients. Data sources: A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption. Study selection and data extraction: Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools. Data synthesis: A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, −13.19 µg kg−1 h−1 morphine equivalents, 95% CI −22.10 to −4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups. Relevance to patient care and clinical practice: This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation. Conclusion: Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations. [ABSTRACT FROM AUTHOR]

trans-Ferulic acid (TFA), a bioactive compound found in many plants, has been recognized for its diverse pharmacological activities, including potential neurological benefits. Previous studies suggest that TFA exerts anxiolytic effects via GABAergic pathways. This study aimed to investigate the sedative effects of TFA and its possible molecular mechanisms through in vivo and in silico approaches. Adult Swiss mice were randomly divided into six groups (n = 7): control (vehicle), standard (DZP: Diazepam at 3 mg/kg, p.o.), three test groups (TFA at 25, 50, and 75 mg/kg, p.o.), and a combination group (TFA: 50 mg/kg with DZP: 3 mg/kg, p.o.). Thirty minutes post-treatment, thiopental sodium (TS) at 40 mg/kg was administered to induce sedation, and latency as well as duration of sleep, were observed for up to 4 h. In silico studies were conducted with GABA A receptor subunits (α1 and β2) to elucidate the possible molecular interactions. The results demonstrated that TFA significantly reduced latency and extended sleep duration in a dose-dependent manner compared to the control. Additionally, TFA combined with DZP further significantly (p < 0.001) enhanced these effects. In silico analysis revealed that TFA and DZP exhibited strong binding affinities with the GABA A receptor subunits (α1 and β2) in the identical binding sites, with binding energies of -6.8 and - 8.7 kcal/mol, respectively. Collectively, TFA exerted a mild sedative effect in TS-induced sleeping mice and modulated the activity of DZP, likely through interactions with GABA A receptors. TFA showed promising activity as a potential candidate for managing sleep disorders such as insomnia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Md. Shimul Bhuia reports was provided by Bangabandhu Sheikh Mujibur Rahman Science and Technology University. Md. Shimul Bhuia reports a relationship with Bangabandhu Sheikh Mujibur Rahman Science and Technology University that includes: non-financial support. Md. Shimul Bhuia has patent N/A pending to N/A. Not applicable., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Appropriate sedative and analgesic selection is essential to reduce patient discomfort and body movement to safely conduct endoscopic ultrasonography (EUS). However, few cases have examined sedation with propofol in EUS, and few studies the need for combined analgesia. In this study, we retrospectively evaluated the usefulness and safety of propofol without analgesics for sedation in biliopancreatic observational EUS., Methods: This single-center retrospective study included 516 observational biliopancreatic EUS procedures using propofol alone performed between April 2021 and March 2023. The primary and secondary endpoints were the observational biliopancreatic EUS results obtained with propofol alone and adverse event occurrence, respectively., Results: The median examination time and total propofol dose were 22 (range: 10-67) min and 186.5 (range: 50-501) mg, respectively. The median starting Richmond Agitation-Sedation Scale and Visual Analog Scale scores were -5 (range: -5-1) and 0 (range: 0-10), respectively. The median recovery time was 22 (range: 5-80) min. Adverse events occurred in 60 (11.6%) patients. Trainee-performed examination (odds ratio [OR] 3.52, 95% confidence interval [CI]: 1.63-7.60, p = 0.0014) and examination length (>22 min; OR 1.67, 95% CI: 0.95-2.92, p = 0.07) were risk factors for adverse events.High body mass index (OR 1.87, 95% CI: 1.10-3.16, p = 0.02) and extended examination time (OR 4.23, 95% CI: 2.08-8. 57, p < 0.001) were risk factors for delayed recovery., Conclusions: During observational biliopancreatic EUS, propofol is useful as a single sedative and offers high patient satisfaction and relative safety., Competing Interests: Haruhiro Inoue, who received grants from the Olympus Corporation and Takeda Pharmaceutical Company, is an advisor for Olympus Corporation and Top Corporation. The other authors declare no conflict of interest., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing., Objective: The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation., Methods: Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale-Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale-Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care., Results: The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026., Conclusions: The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones., Trial Registration: Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889., International Registered Report Identifier (irrid): DERR1-10.2196/55129., (©Benjamin Thomas, Greg Barclay, Wing-Shan Angela Lo, Judy Mullan, Kylie Mansfield. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.09.2024.)

Barbiturates and benzodiazepines are GABAA-receptor agonists and potent antiseizure medications. We reported that exposure of neonatal macaques to combination of phenobarbital and midazolam (Pb/M) for 24 h, at clinically relevant doses and plasma levels, causes widespread apoptosis affecting neurons and oligodendrocytes. Notably, the extent of injury was markedly more severe compared to shorter (8 h) exposure to these drugs. We also reported that, in the infant macaque, mild hypothermia ameliorates the apoptosis response to the anesthetic sevoflurane. These findings prompted us explore whether mild hypothermia might protect infant nonhuman primates from neuro- and gliotoxicity of Pb/M. Since human infants with seizures may receive combinations of benzodiazepines and barbiturates for days, we opted for 24 h treatment with Pb/M.Neonatal rhesus monkeys received phenobarbital intravenously, followed by midazolam infusion over 24 h under normothermia (T > 36.5 °C-37.5 °C; n = 4) or mild hypothermia (T = 35 °C-36.5 °C; n = 5). Medication doses and blood levels measured were comparable to those in human infants. Animals were euthanized at 36 h and brains examined immunohistochemically and stereologically.Treatment was well tolerated. Extensive degeneration of neurons and oligodendrocytes was seen at 36 h in both groups within neocortex, basal ganglia, hippocampus and brainstem. Mild hypothermia over 36 h (maintained until terminal perfusion) conferred no protection against the neurotoxic and gliotoxic effects of Pb/M. This is in marked contrast to our previous findings that mild hypothermia is protective in the context of a 5 h-long exposure to sevoflurane in infant macaques.These findings demonstrate that brain injury caused by prolonged exposure to Pb/M in the neonatal primate cannot be ameliorated by mild hypothermia.

Background and Aim: The efficacy of intranasal (IN) dexmedetomidine in cats as a premedication remains elusive. Thus, this study aimed to compare the perioperative and sparing effects of IN and intramuscular (IM) dexmedetomidine administration on propofol requirements for anesthetic induction in cats. Materials and Methods: This study randomly assigned 16 cats into two groups of IN or IM dexmedetomidine at 20 μg/kg. Sedation scores and side effects were recorded at time points of 0, 5, 10, 15, and 20 min after the dexmedetomidine administration. Anesthesia was induced with intravenous (IV) 1% propofol by titrating a bolus of 2 mg every 45 s and the total dose of the administered IV propofol to achieve endotracheal intubation was recorded. Results: Cats receiving IM dexmedetomidine were significantly associated with higher sedation scores. All cats were sedated at 20 min after premedication; however, the average composite sedation scores in the IN group were significantly lower than those in the IM group during premedication. Pre-operative side effects, including vomiting, were more frequently observed in the IN group (5 cats, 62.5%) than in the IM group (3 cats, 37.5%; p < 0.05). Higher body temperature (>1°F compared to baseline) was more frequently observed in the IN group (6 cats, 75.0%) than in the IM group (1 cat, 12.5%; p < 0.05). The dosage of required propofol in the IN group was significantly higher (1.1 ± 0.3 mg/kg) than that in the IM group (0.7 ± 0.2 mg/kg; p < 0.05). The duration of general anesthesia was comparable between the groups. Conclusion: IN dexmedetomidine produces moderate sedation and cats may have side effects, including vomiting and higher body temperature. Higher sparing effects of propofol were identified in the IM group compared with the IN group. Nonetheless, IN administration of dexmedetomidine provides a noninvasive alternative to the IM route. [ABSTRACT FROM AUTHOR]

Background: The use of MV can easily lead to VAP especially in ICU patients. SUP, sedatives, statin and insulin have been proved to prevent VAP and improve the prognosis of patients. Our aim was to analyze the effects of SUP, sedative, statin, and insulin on patients with MV. Methods: The occurrence of VAP and death in MV patients and VAP patients were explored by multivariate logistic regression and Cox regression to analyze analyses. Results: Totally, 5277 cases who received MV in ICU from MIMIC IV database were included. There were 826 (15.7%) cases in VAP-group and 4451 (84.3%) cases in non-VAP group and there were 1914 (36.3%) cases in hospital mortalities altogether. No protective effect of drugs on VAP was found in MV patients. The risk of death was 1.43 times higher in MV patients taking midazolam than in propofol (aHR = 1.43 95% CI: 1.04,1.97). No protective effect of drugs on death was found in VAP patients. Conclusion: Compared with midazolam, propofol is more recommended as sedation regimen in ICU patients with MV. Further high-quality studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that dexmedetomidine improves neurological function. Whether dexmedetomidine reduces mortality or improves quantitative electroencephalography (qEEG) among patients post-craniotomy remains unclear. Methods: This single-center randomized study was conducted prospectively from 1 January 2019 to 31 December 2020. Patients who were transferred to the ICU after craniotomy within 24 h were included. The analgesic was titrated to a Critical care Pain Observation Tool (CPOT) score ≤2, and the sedative was titrated to a Richmond Agitation–Sedation Scale (RASS) score ≤−3 for at least 24 h. The qEEG signals were collected by four electrodes (F3, T3, F4, and T4 according to the international 10/20 EEG electrode practice). The primary outcome was 28-day mortality and qEEG results on day 1 and day 3 after sedation. Results: One hundred and fifty-one patients were enrolled in this study, of whom 77 were in the dexmedetomidine group and 74 in the midazolam group. No significant difference was found between the two groups in mortality at 28 days (14.3% vs. 24.3%; p = 0.117) as well as in the theta/beta ratio (TBR), the delta/alpha ratio (DAR), and the (delta + theta)/(alpha + beta) ratio (DTABR) between the two groups on day 1 or day 3. However, both the TBR and the DTABR were significantly increased in the dexmedetomidine group. The DTABR in the midazolam group was significantly increased. The DAR was significantly increased on the right side in the dexmedetomidine group (20.4 (11.6–43.3) vs. 35.1 (16.7–65.0), p = 0.006) as well as on both sides in the midazolam group (Left: 19.5 (10.1–35.8) vs. 37.3 (19.3–75.7), p = 0.006; Right: 18.9 (10.1–52.3) vs. 39.8 (17.5–99.9), p = 0.002). Conclusion: Compared with midazolam, dexmedetomidine did not lead to a lower 28-day mortality or better qEEG results in brain injury patients after a craniotomy. [ABSTRACT FROM AUTHOR]

Micromeria biflora, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of Micromeria biflora led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety. [ABSTRACT FROM AUTHOR]

OBJECTIVE: While trazodone is approved for the treatment of depression, the off-label use of this medication for insomnia has surpassed its usage as an antidepressant. In this systematic review, we examined the evidence for the efficacy and safety of trazodone for insomnia. METHODS: A literature search was conducted using MEDLINE/PubMed databases from the past 33 years (1983-2016) and the keywords insomnia, trazodone, sedative, treatment, and hypnotics. The results were restricted to English language and human subjects. All randomized clinical trials, meta-analyses, observational studies, and placebo-controlled trials regarding trazodone for the treatment of primary or secondary insomnia were reported, per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The study selection process yielded a total of 45 studies. RESULTS: Evidence for the efficacy of trazodone has been repeatedly demonstrated for primary insomnia, as well as secondary insomnia, including for symptoms that are a result of depression, dementia, and being a healthy man. Earlier studies (1980-2000) focused on utilizing trazodone at high doses (≥100mg/d) for the treatment of insomnia among the depressed population; however, since the 2000s, the utility of trazodone has been expanded to treat secondary insomnia among the non-depressed population as well. The side effects are dose-dependent, and the most common is drowsiness. CONCLUSION: A review of the literature suggests that there are adequate data supporting the efficacy and general safety of the low-dose use of trazodone for the treatment of insomnia.

Insomnia is one of the most prevalent sleep disorders worldwide which significantly affects the quality of life. Pharmacological and non-pharmacological approaches have been applied in managing insomnia. The risk of tolerance and dependence on conventional medications and their other side effects leads the surveys to complementary and alternative medicine. This overview aimed to compile the clinical trials on herbal remedies in managing insomnia for facilitating future studies on medicinal plant in this issue. The keywords “Medicinal plant”, “Herbal medicine” in combination with “Hypnotic and sedative”, "Insomnia" or "Sleep" were searched through PubMed, Google Scholar, and Scopus electronic databases from 1st January 2000 to 31st August 2020. Then, all clinical trials focusing on the efficacy of medicinal plants on insomnia were collected. Based on the inclusion and exclusion criteria, 36 articles were selected, included 16 medicinal plants (23 studies) as a single herb and 13 polyherbal formulations. The most prevalent route of administration among these trials was oral. Matricaria chamomilla L., Valeriana officinalis L., Viola odorata L., and Passiflora incarnata L. were among the most prevalent effective herbal medicines on insomnia. Also, the modulation of the GABAergic system was the most common target of these medicinal plants. Herbal remedies can be introduced as safe and effective alternatives for conventional medications in managing insomnia. The popular herbal medicines, such as M. chamomilla, V. officinalis, V. odorata, are suitable for further therapeutic development. Other cited medicinal plants in this review can be more investigated in improvement of sleep.

Background: The use of MV can easily lead to VAP especially in ICU patients. SUP, sedatives, statin and insulin have been proved to prevent VAP and improve the prognosis of patients. Our aim was to analyze the effects of SUP, sedative, statin, and insulin on patients with MV.Methods: The occurrence of VAP and death in MV patients and VAP patients were explored by multivariate logistic regression and Cox regression to analyze analyses.Results: Totally, 5277 cases who received MV in ICU from MIMIC IV database were included. There were 826 (15.7%) cases in VAP-group and 4451 (84.3%) cases in non-VAP group and there were 1914 (36.3%) cases in hospital mortalities altogether. No protective effect of drugs on VAP was found in MV patients. The risk of death was 1.43 times higher in MV patients taking midazolam than in propofol (aHR = 1.43 95% CI: 1.04,1.97). No protective effect of drugs on death was found in VAP patients.Conclusion: Compared with midazolam, propofol is more recommended as sedation regimen in ICU patients with MV. Further high-quality studies are needed to confirm this finding.

[Display omitted] • The best synergistic effect was found at a ratio of 5:1 (jujuboside B: spinosin). • The combination of jujuboside B and spinosin significantly improve the insomnia. • The combination regulate the content of neurotransmitters and inflammatory factors. • The combination significantly regulate the expression of various proteins. The seeds of Ziziphus jujuba contains more than 150 compounds, such as jujuboside B and spinosin as the major components, showing bioactivities. In this study, jujuboside B and spinosin were tested for their neuroprotective and sedative effect via cell experiments and their best synergistic effect was found at a ratio of 5:1 (jujuboside B: spinosin). Molecular docking results showed that jujuboside B and spinosin had good binding ability with receptor proteins, namely GABAAR-α1, GABABR-1, GAD-67, and GAT-1. In the follow-up animal experiments, the optimum combination of jujuboside B and spinosin (5:1) was able to improve the sleep by up-regulating the expression of GABAAR-α1, GABABR-1, and GAD-67, while down-regulating the expression of GAT-1. This study confirmed the combined neuroprotective and sedative effects of jujuboside B and spinosin. [ABSTRACT FROM AUTHOR]

Aromas have a powerful influence in our everyday life and are known to exhibit an array of pharmacological properties, including anxiolytic, anti-stress, relaxing, and sedative effects. Numerous animal and human studies support the use of aromas and their constituents to reduce anxiety-related symptoms and/or behaviours. Although the exact mechanism of how these aromas exert their anxiolytic effects is not fully understood, the GABAergic system is thought to be primarily involved. The fragrance emitted from a number of plant essential oils has shown promise in recent studies in modulating GABAergic neurotransmission, with GABAA receptors being the primary therapeutic target. This review will explore the anxiolytic and sedative properties of aromas found in common beverages, such as coffee, tea, and whisky as well aromas found in food, spices, volatile organic compounds, and popular botanicals and their constituents. In doing so, this review will focus on these aromas and their influence on the GABAergic system and provide greater insight into viable anxiety treatment options. [ABSTRACT FROM AUTHOR]

Background: Children often require sedation for long non-invasive diagnostic procedures. Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist with sedative, anxiolytic and analgesic properties. It mimics natural sleep and allows patients to easily arouse with minimal effects on respiration and airway patency. Objective: To assess the successful completion of pediatric non-invasive diagnostic procedures with intranasal dexmedetomidine as a sedative agent. Methods: Seventy-nine subjects of age six months to twelve years scheduled for non-invasive diagnostic procedures were included. Dexmedetomidine (4 mcg/kg) was administered intranasally 25 minutes before the scheduled time of procedure. A sedation score of two or above as per the MICHIGAN sedation scale was considered satisfactory for starting the procedure. Results: Seventy-four (95%) out of the seventy-nine subjects were successfully sedated with Intranasal dexmedetomidine (p<0.0001). The mean time and Standard deviation to achieve sedation was 18.9 ± 2.82 mins. The median time was 19 mins with a range from 15-25 minutes. Post anesthesia discharge time for Intranasal dexmedetomidine was 20 minutes with zero incidence of post procedure nausea and vomiting. Conclusions: Intranasal dexmedetomidine can be used as an alternative to General anesthesia for non-invasive diagnostic procedures outside operating room with less adverse effects in this cohort. [ABSTRACT FROM AUTHOR]

A drug that subdues exhilaration and produces a calming effect in the subject without necessarily inducing sleep is referred to as sedative. The main system for action of these drugs is the Central Nervous System (CNS). Sedatives are slow working drugs with a levelled dose response curve. They act by modifying nerve responses in CNS to the brain which slows down brain activity thus relaxing the body. Gamma-amino-Butyric acid (GABA) is neurotransmitter which is responsible for retarding the brain functioning and sedatives increase the activity of GABA to produce more effect on the brain activity. Mostly sedatives are used to treat sleep disorders, pain or as anaesthetics. Opioids are sedatives used to treat pain, but long-term usage of these drugs leads to dependency and addiction which may be a challenge to treat. People experience withdrawal symptoms like nausea, vomiting, anxiety, insomnia and/or irritability along with seizures and loss of consciousness in some extreme cases. BXCL501 is a formulation of Dexmedetomidine used to treat agitation and symptoms of opioid withdrawal. The drug is designed in such a manner that it reduces agitation but does not produce excessive sedation. The RELEASE clinical trial of "bioxcel therapeutics" lead to the use of this drug to treat or retard opioid withdrawal symptoms and agitations. This article is aimed at reviewing and summarising existing data concerning the synthesis, chemical taxonomy, properties, mechanism of action, pharmacokinetic-pharmacodynamic profile, side effects, interactions, toxicology of dexmedetomidine. [ABSTRACT FROM AUTHOR]

Background: Ayurvedic pharmacopoeia records vivid indications of Cannabis (Bhanga) including its analgesic, sedative and intoxicant actions. For inhibition of intoxication, Ayurveda recommends certain processing (Shodhana) techniques for Cannabis. The present study is planned to evaluate the analgesic potential and sedative effects of water washed (Jalaprakshalana)–processed Cannabis sativa leaves through pharmacological experimentation. Methods: Wistar strain albino rats weighing 200 ± 20 g and Swiss albino mice (25–35 g) of either sex were used in the study. Pharmacologically validated models were used to evaluate the analgesic effects (by formalin test and tail flick method) and neuromuscular coordination by rotarod experiment. water-washed–processed Cannabis leaves powder (test drug [TD]) was administered at dose of 22.5 and 45 mg/kg for rat and mouse, respectively, against reference standard morphine sulfate (MS) 5 mg/kg and the results were evaluated statistically. Results: TD at 22.5 and 45 mg/kg showed significant decrease in paw licking response at early phase in formalin test. TD at 22.5 mg/kg showed significant increase in tail flick latency after 3 h, and in 45 mg/kg dose, it was significant up to 4 h. In rotarod experiment, TD did not show any decrease in latency of fall-off time after 1 and 3 h. Conclusion: Water-washed processed Cannabis leaves powder possesses significant analgesic effect at 22.5 mg/kg (250 mg human dose) and 45 mg/kg (500 mg human dose) comparable to MS 5 mg while nonsignificant effect in neuromuscular in-coordination, thus devoid of sedative effect.

The biological and pharmacological properties of natural polyphenols of the extract of Euterpe oleracea stone (EEOS) are associated with the central nervous system (CNS). To investigate the sedative and myorelaxant activity of EEOS in vivo, this study aimed to present the myorelaxant and sedative effects of EEOS in Wistar rats using spontaneous locomotor activity and motor electrophysiology. A total of 108 animals were used in the following experiments: a) behavioral tests (n = 27); b) electromyographic recordings of skeletal muscle (n = 27); c) respiratory muscle activity recordings (n = 27); d) cardiac muscle activity recordings (n = 27). The behavioral characteristics were measured according to the latency time of onset, the transient loss of posture reflex and maximum muscle relaxation. Electrodes were implanted in the gastrocnemius muscle and in the tenth intercostal space for electromyographic (EMG) signal capture to record muscle contraction, and in the D2 lead for electrocardiogram acquisition. After using the 300 mg/kg dose of EEOS intraperitoneally, a myorelaxant activity exhibited a lower frequency of contractility with an amplitude pattern of low and short duration at gastrocnemius muscle and intercostal muscle, which clearly describes a myorelaxant activity and changes in cardiac activity. The present report is so far the first study to demonstrate the myorelaxant activity of this extract, indicating an alternative route for açai stone valorization and its application in pharmaceutical fields.

Senna bicapsularis is an important medicinal plant that has been traditionally used as a purgative and muscle relaxant as well as for the treatment of pain. The current work focused on phytochemicals to explore the analgesic, muscle relaxant, sedative and toxicological effects of the aerial part of Senna bicapsularis in an animal model. An acetic-acid-induced writhing screening showed that pretreatment of methanolic, ethyl acetate and aqueous extracts exhibited excellent analgesic activity at 500 mg/kg i.p. In chimney and traction, the crude butanolic and aqueous extracts showed a promising muscle relaxation effect at 500 mg/kg i.p., while the sedative effect of the ethyl acetate and methanolic extracts exhibited good activity at 500 mg/kg i.p. Crude extracts of S. bicapsularis were assessed for anti-inflammatory potency during a 5-h experiment, and the ethanolic and methanolic extract exhibited excellent inhibition in carrageenan-induced paw oedema among entire extracts. These provided natural products chemists for the treatment of pain and relaxation of muscles.

ObjectiveThe present study is designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a cesarean section.MethodsA total of 60 puerperae undergoing a cesarean section recruited from a single center were divided into three groups according to the postoperative continuous analgesia protocol: control group (100 mL of normal saline containing 10 µg/kg fentanyl and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), DB1 group (100 mL of normal saline containing 1.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), and DB2 group (100 mL normal saline containing 2.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h). We compared the blood pressure, heart rate, oxygen saturation, VAS score, Ramsay score, and adverse reactions of puerperae among the three groups after surgery.ResultsThe baseline data all have no significant difference in the three groups (p > 0.05). Compared with those in the control group, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB1 group and DB2 group were significantly decreased at 6, 24, and 48 h (P 0.05).ConclusionDexmedetomidine combined with butorphanol can improve the analgesic and sedative effects in continuous analgesia after a cesarean section, and the analgesic and sedative effects of dexmedetomidine in the high-dose group are better than those in the low-dose group.

Nicotinamide mononucleotide (NMN) has various beneficial effects, while its protective effects against insomnia remain elusive. NMN and NMN-rich products (NMNP) alleviated depression-like behavior and stimulated sodium pentobarbital-induced sleeping of p-chlorophenylalanine (PCPA)-induced mice. NMN and NMNP restored brain damages and reduced oxidative stress. NAD+ concentration, silent mating type information regulation 2 homolog 1 (SIRT1) expression, 5-hydroxytryptamine (5-HT) level and 5-HT1A expression in hippocampus of PCPA-induced mice were up-regulated by NMN and NMNP. NMN and NMNP also modulated γ-gminobutyric acid (GABA) and glutamate production by increasing GABAA receptor α2 and glutamic acid decarboxylase 65/67 expression. NMNP, composed 23.9% of NMN, was more powerful than NMN in activating GABAergic system. NMN and NMNP exhibited prominent enhancement on immune system through boosting NO secretion and IL-1β expression. These data suggested that NMN and NMNP exerted sedative effects via regulating oxidative stress, SIRT1 pathway, 5-HTergic, GABAergic and immune systems simultaneously.

Limited epidemiological national data are available for anxiolytic, sedative, or hypnotic drug (ASH) use disorder hospitalizations. To examine the time-trends in and outcomes of ASH use disorder hospitalizations. Rates of ASH use disorder hospitalizations and associated healthcare utilization and mortality were examined using the U.S. National Inpatient Sample data (NIS) from 1998 to 2014. Multivariable-adjusted logistic regression assessed the association of demographic, medical comorbidity (using validated composite score of 17 conditions, the Deyo-Charlson index), and hospital characteristics with healthcare utilization (total hospital charges, length of hospital stay [LOS], and discharge to a non-home setting) and inpatient mortality for hospitalizations with ASH use disorder. There were an estimated 1,171,673 weighted ASH use disorder hospitalizations. The ASH use disorder hospitalization rates increased 3.12-fold from 96 to 299 per 100,000 NIS hospitalizations from 1998–2000 to 2013–2014. In the same period, associated non-home discharge rate increased 3.33-fold from 12.9 to 43 and in-hospital mortality rate increased 3.17-fold from 0.46 to 1.46 per 100,000 (all p values ≤.002). In the multivariable-adjusted analyses, older age, black race/ethnicity, Deyo-Charlson index score of 2 or higher, non-private insurance payer, higher income, hospital region, urban setting hospital and a larger hospital bed size, were significantly associated with higher healthcare utilization outcomes and/or mortality. Female sex was associated with higher healthcare utilization outcomes, but lower in-hospital mortality. This study confirmed the rising ASH use disorder hospitalization burden in the United States. An increasing inpatient mortality and non-home discharge rate for hospitalizations with ASH use disorder are concerning. The identification of modifiable and non-modifiable risk factors associated with outcomes should allow prognostication and designing of interventions to improve outcomes. [ABSTRACT FROM AUTHOR]

This study deals with facile and rapid synthesis of silver nanoparticles (AgNPs) and Gold nanoparticles (AuNPs) using Mentha longifolia leaves extracts (MLE). The synthesized AgNPs and AuNPs were characterized by UV-visible spectroscopy (UV-Vis), Fourier transformed infra-red spectroscopy (FT-IR), atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. The phytochemical analysis showed the presence of bioactive secondary metabolites, which are involved in the synthesis of nanoparticles (NPs). The surface plasmon resonance (SPR) observed at 435 and 550 nm, confirmed the green synthesis of AgNPs and AuNPs, respectively. The TEM images showed poly dispersed and round oval shapes of Ag and Au NPs with an average particles size of 10.23 ± 2 nm and 13.45 ± 2 nm, respectively. TEM results are in close agreements with that of AFM analysis. The FT-IR spectroscopy revealed the presence of OH, –NH2 and C = O groups, which involved in the synthesis of NPs. The MLE and their AgNPs and AuNP exhibited good in vitro antibacterial and anti-oxidant activities. Moreover, MLE and NPs also showed in vivo analgesic activities in mice, and excellent sedative properties in open field test paradigm. [ABSTRACT FROM AUTHOR]

Premedication is an important part of preoperative management of all patients. It involves the optimization of underlying medical conditions and implementation of risk reduction therapies. Anxiolytic medications still have a place, particularly in certain patient populations. Important classes of drugs to consider in the perioperative period are cardiovascular drugs, anticoagulants and antiplatelets. Aspiration prophylaxis is the main risk-reduction therapy used. Benzodiazepines are still the mainstay of anxiolysis treatment, while topical anaesthesia can be used to aid cannula insertion. The most important aspect is thorough assessment of each patient, and tailoring the premedication to their specific needs. [ABSTRACT FROM AUTHOR]

Although older adult prescription drug misuse (PDM) is associated with concerning consequences, stimulant PDM and poly- PDM involving multiple medication classes each remain understudied. Our objectives were to examine PDM and poly-PDM prevalence by medication class in US older adults and to identify the mental health, SUD, and health-related quality-of-life correlates of poly-PDM. Data were from adults 50 and older completing the National Epidemiologic Survey on Alcohol and Related Conditions-III, (N = 14,667). Prevalence of PDM and poly-PDM by medication class was estimated. Logistic regression established odds of four SUD diagnoses, five psychopathology diagnoses and lifetime suicide attempts; linear regression evaluated health-related quality-of-life by PDM/poly-PDM status. Past-year PDM abstinence increased with age (50–54 years: 80.5%; 80 and older: 96.0%), while poly-PDM declined; past-year stimulant PDM was rare (≤0.6%), except when combined with opioid and tranquilizer/sedative PDM. Compared to no past-year PDM, both past-year opioid-only PDM and opioid-involved poly-PDM were associated with poorer health-related quality-of-life and greater odds of psychopathology and SUD, with the highest odds in poly-PDM. The presence of any opioid-involved PDM in older adults highlights screening for SUD, psychopathology, and other medical conditions, with the most significant intervention needs likely in those with opioid-involved poly-PDM. [ABSTRACT FROM AUTHOR]

Neurodiagnostic investigation requirements are expanding for diagnostic and therapeutic purposes in children, especially in those with developmental delay/intellectual disability (DD/ID). Thus, determination of optimal sedatives to achieve successful sedation and immobility without further neurological compromise is important in children with DD/ID. The purpose of this study is to assess the effectiveness and adverse reactions of chloral hydrate (CH) for brain magnetic resonance imaging (B-MRI) in children with DD/ID compared to those with normal intelligence (NI). We performed a retrospective chart review of children aged from 1 day to 12 years who required elective sedation using CH for B-MRI. About 730 cases (415 with DD/ID and 315 with NI) of CH sedation were conducted for B-MRI. Children with DD/ID showed a higher failure rate (22%) than did those with NI (6%); additional CH and prolonged sedation time were required. There was no difference in incidence of adverse reactions between DD/ID and NI groups (p = 0.338). Older or heavier children with DD/ID (p = 0.036 and p = 0.013, respectively), as well as those diagnosed with epilepsy or neuropsychiatric disorders showed higher risk of sedation failure (p < 0.001 for each). In conclusion, CH was a suboptimal sedative drug for children with DD/ID compared with those with NI. Other alternative or supplementary sedatives should be taken into consideration especially for those vulnerable groups. [ABSTRACT FROM AUTHOR]

Background/Aims In this study, we compared the efficacy and safety of etomidate with those of propofol or midazolam for the maintenance of sedation during endoscopy. Methods The study enrolled patients who underwent sedative endoscopy in our hospital and divided them into three groups. Patients in each group were administered midazolam as induction therapy and were subsequently administered either midazolam (M + M group), propofol (M + P group), or etomidate (M + E group) as maintenance medication. The primary outcome was overall cardiovascular and respiratory adverse events. Results In total, 105 patients who underwent sedative endoscopic examination were enrolled. The outcomes related to the procedure and sedation were not significantly different among the groups. Overall cardiovascular and respiratory adverse events were observed in 9 patients (25.7%) in the M + M group, 8 patients (23.5%) in the M + P group, and 10 patients (27.8%) in the M + E group. The logistic regression analysis revealed that etomidate use was not an independent risk factor for overall cardiovascular and respiratory adverse events. Conclusions The outcomes following the use of etomidate for maintenance after induction with midazolam for sedation in upper gastrointestinal endoscopy were not inferior to those following midazolam or propofol use from the perspectives of safety and efficacy.

The water-soluble extract is a gummy semi-solid content of Apis cerana indica beehive (WSE-BH). The present study reports the neuropharmacological effects of beehive derived from Apis cerana indica with brine shrimp lethality bioassay. The neuropharmacological results evaluated by modified open field, hole cross, elevated plus maze and hole board (OF-HC-EPM-HBT) test by Swiss Albino mice of both sexes after single oral administration where parameters for sedative and anxiolytic activity was square movements, hole crossing, time spent in open arm and head dipping which is the unpunished or unlearned response. A time-dependent manner activity observed by WSE-BH (200 and 400 mg/kg) and diazepam (1 mg/kg) against negative control normal saline. At low dose (200 mg/kg), the OF and HC possess significant reducing effects in time dependence manner while EPM and HBT exhibited significant anxiolytic activity avoiding sedation, whereas at 400 mg/kg exhibited an irregular effect. The current results were suggesting that WSE-BH might a good source of anxiolytic and sedative effects at low dose concentration. [ J Adv Biotechnol Exp Ther 2020; 3(2.000): 128-134]

OBJECTIVE: This study aimed to investigate a prospective association between shift work and use of psychotropic medicine. METHODS: Survey data from random samples of the general working population of Denmark (N=19 259) were linked to data from national registers. Poisson regression was used for analyses of prospective associations between shift work and redeemed prescriptions of psychotropic medicine. Prevalent cases were excluded at baseline. In secondary analyses, we tested differential effects on subsets of psychotropic medicine and, cross-sectionally, we studied correspondence between estimates based on psychotropic medicine and self-reported mental health. According to the protocol we interpret results from the secondary analyses following the principles for nested hypothesis testing, if the primary analyses reject the null-hypothesis, and otherwise we regard it as hypothesis generating exploratory analyses. RESULTS: In the primary analysis, the rate ratio for incidence of psychotropic medicine among shift workers was 1.09 (95% confidence interval 0.99–1.21). Results from the secondary analyses suggested increased incidence of use of hypnotics, sedatives and antidepressants and decreased incidence of use of anxiolytics. Cross-sectional analysis suggested increased risk for use of psychotropic medicine (all kinds), but not for poor self-rated mental health. CONCLUSIONS: Results did not support that working in shifts to the extent that is currently practiced in Denmark is associated with an increased incidence of overall psychotropic medicine use. Future studies should test, whether there is a differential incidence for different drugs among shift workers as suggested by the secondary analyses and how psychotropic medicine use and mental health are related.

Abstract Background Spathodea campanulata P. Beauv. (Bignoniaceae) is a very common plant in Bangladesh which is locally called “Rudrapalash”. In Nigeria leaves extract of S. campanulata has a reputation of being used as an anticonvulsant. In this connection, the aim of this study was to investigate other neuropharmacological effects like sedative and anxiolytic activities of methanol extract of S. campanulata (MESC) leaves in different mice tests. Methods To assay sedative activity mice were subjected to open field and hole-cross test, whereas anxiolytic activity was checked by the elevated-plus maze, light-dark box, and hole-board test. For each test, mice were divided into control group (deionized water, 0.1 ml/mouse, p.o.), standard group (diazepam, 1 mg/kg, i.p) and three test groups (200, 400 and 600 mg/kg MESC, p.o.). The acute toxicity test and phytochemical screening of MESC were performed before the pharmacological study. Results The result demonstrated strong sedative and anxiolytic activity of MESC in a dose-dependent manner. All doses of MESC (200, 400 & 600 mg/kg) reduced the number of (square & hole) crossed by mice in both open field and hole cross tests (p

Hospital wastewater is one of the most infectious and dangerous wastewaters that may contain large amounts of pathogenic microorganisms, dangerous pollutants of various hormones. More than 80 different types of drugs have been found that are not completely eliminated in biological processes and reach the receiving water. In this study, one of the important hospitals of Tehran, in a crowded area with high volume of referrals, was investigated. The purpose of this study was to investigate the possibility of drugs, especially sedative drug compounds, in hospital treated wastewater. For this purpose, instant sampling was carried out three times from the effluent of the hospital wastewater treatment plant and the samples were conditioned using solid phase extraction (SPE) method. The extracted materials were measured by HPLC equipped with UV and FLD detectors, resulting in the identification of various sedatives (including Diazepam, Oxazepam, Lorazepam, Alprazolam Clonazepam, Chlordiazepoxide, and Bromazepam). The mean concentration of sedatives in the January sampling showed that the highest concentration observed for Lorasepam with a mean of 0.15 ng/l and the lowest one for Chlordiazepoxide with a mean of 0.02 ng/l. The highest and lowest concentrations measured in February were 0.15 and 0.02 ng/l for Lorasepam and Chlordiazepoxide respectively.

Aim Accurately calculating the Sequential Organ Failure Assessment (SOFA) score is essential for medical resource allocation and decision‐making. This study surveyed Japanese intensive care units regarding their assessment of the Glasgow Coma Scale (GCS) and PaO2/FIO2 ratio, components of the SOFA score. Methods A cross‐sectional, web‐based survey was conducted among healthcare workers. The survey consisted of questions about the intensive care units where they work and questions for respondents. It was distributed to healthcare workers by e‐mail through the Japanese Society of Intensive Care Medicine mailing list and social networking service. Results Among 414 responses, we obtained 211 valid responses and 175 survey results from unique intensive care units. When assessing GCS in patients under the influence of sedatives, 45.1% (95% confidence interval, 37.6–52.8) of intensive care units assessed GCS assuming that the sedatives had no influence. For the PaO2/FIO2 ratio in the SOFA score, calculation based on the Japanese Intensive Care Patient Database definition document and mechanical ventilator settings were the most common methods in patients with oxygen masks and on extracorporeal membrane oxygenation, respectively. Approximately 60% of respondents indicated that it was difficult to assess GCS assuming that sedatives had no influence. Conclusion In patients under the influence of sedatives, approximately half of the intensive care units assessed assumed GCS. There was variation in the methods used to assess the PaO2/FIO2 ratio. Standardized assessment methods for GCS and the PaO2/FIO2 ratio are needed to obtain valid SOFA score.

Ciprofol (HSK3486) is a novel intravenous anaesthetic developed as an alternative to propofol, offering a safer and more effective option in anaesthesia. It works primarily by modulating the gamma-aminobutyric acid (GABA) receptors in the central nervous system, leading to sedation and hypnosis. Ciprofol's unique pharmacological properties include a rapid onset of action, shorter duration, and reduced cardiovascular and respiratory depression compared to propofol, making it particularly suitable for outpatient and day surgery procedures. Molecular changes in ciprofol appear to be superior to those of other cibenzolines; it is more potent and has a stable hemodynamic effect. It has been used in primary surgery, inpatients and outpatients, and even for sedation of intensive care patients. The reported clinical data indicate that ciprofol is a powerful sedative that is characterised by a high-enough speed of emergence from the state of anaesthesia, which is necessary for outpatient conditions and intensive operating modes. It can be considered a new and important perspective in the technology of intravenous anaesthetics with its improved pharmacological characteristics and clinical effects. With the further accumulation of clinical data, ciprofol will undeniably become an essential agent in today's anaesthetic practice and contribute to an enhancement of healthcare efficiency by providing a more secure approach to numerous kinds of surgical interventions. The purpose of the current study is to provide a review of the pharmacology and clinical use of ciprofol, a new intravenous anaesthetic agent. Various studies demonstrate the functionality and safety profile of ciprofol, which solidifies it as a potential contender for propofol. Regarding respiratory depression, hypoxemia, and injection pain during hysteroscopy, ciprofol was shown to be a relatively safer option than propofol. Ciprofol can, therefore, be recommended for intravenous anaesthesia because of its effectiveness and safety, which has been clearly demonstrated. Randomised trials uniformly report the ability to achieve quicker onset of sedation and lower risk with the agent compared to propofol. These findings imply that ciprofol has many benefits concerning a variety of applications in patients due to a lower rate of adverse reactions and increased patient comfort., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Petkar et al.)

The World Health Organization reports that 30% of adults worldwide suffer from insomnia, while 10% of people worldwide suffer with various forms of anxiety. The significant negative effects of conventional medications used to treat anxiety and insomnia, such as abuse, addiction, amnesia, and cognitive and sexual dysfunction, have led to an increased preference for naturally derived substances with fewer side effects. Accordingly, in this study, the sedative and anxiolytic effects of n -hexane, ethyl acetate (EtOAc), methanol (MeOH) and water extracts of the aerial parts of Capparis sicula Duhamel., which is used for sedative purposes in folk medicine, were evaluated. To evaluate the sedative and anxiolytic effects of each extract, bioassay systems were used including traction and hole-board tests. The MeOH extract of C. sicula was the most active extract on in vivo traction and hole-board tests compared to Diazepam. From the MeOH extract, major components were isolated, and their structures were identified as three flavonoid glycosides [rutin (1), quercetin-3- O -glucoside (2), and quercetin 3- O -rhamnoside (3)] using spectral techniques. The most abundant component was determined to be rutin, comprising 8 mg/100 mg dry extract in MeOH extract and 76.7 mg/100 mg dry fraction in fraction C using HPLC. The molecular docking studies evaluated the interaction of isolated flavonoid glycosides with the interaction energies and protein-ligand interaction details of the anxiety-related receptors GABAA and GABAB. For the GABAA receptor, quercetin-3- O -glucoside demonstrated the highest docking score. Quercetin-3- O -rhamnoside and rutin also show promising interactions, particularly with the GABAB receptor, highlighting their potential as modulators of these receptors. In conclusion, the use of C. sicula for sedative purposes in folk medicine has been confirmed for the first time by in vivo studies, and its possible active compounds and sedative-anxiolytic mechanism have been determined through phytochemical and in silico studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Karpuz Ağören, Küpeli Akkol, Çelik and Sobarzo-Sánchez.)

Objectives: A relationship between endoscopic submucosal dissection (ESD) and deep vein thrombosis has been recognized. We previously reported that a high corrected midazolam dose (total midazolam dose/initial dose of midazolam used to induce sedation) is related to elevated D-dimer levels after ESD. In this study, the effect of compression stockings (CSs) in preventing thrombosis following ESD under sedation was evaluated by measuring D-dimer levels before and after ESD., Methods: The participants were patients who underwent ESD for upper gastrointestinal tumors during the period between April 2018 and October 2022. Patients with pre-ESD D-dimer levels ≥1.6 µg/m and patients with corrected midazolam doses ≤3.0 were excluded. A retrospective investigation of the relationship between CS use and high post-ESD D-dimer levels (difference in D-dimer levels ≥1.0 µg/mL between before and after ESD) was conducted., Results: There were 27 patients in the non-CS group (NCS) and 33 patients in the CS group. The number of patients with high post-ESD D-dimer levels was 13 (48.2%) in the non-CS group and six (18.2%) in the CS group; the number in the CS group was significantly lower ( p = 0.024). On logistic regression analysis, a relationship was seen between the wearing of CSs and a lower number of patients with high post-ESD D-dimer levels (odds ratio 0.24, 95% confidence interval 0.08-0.79, p = 0.019)., Conclusion: Wearing CSs was related to a lower risk of high post-ESD D-dimer levels. This result suggests that thrombus formation is a cause of elevated D-dimer levels after ESD., Competing Interests: None., (© 2024 The Author(s). DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Despite of being the drugs of the same therapeutic class (Benzodiazepines), each of them shows different actions prominently. It is commonly seen that Bromazepam, Clonazepam, and, Alprazolam are prescribed for the treatment of anxiety disorders, panic disorders, and phobias. On the other hand, Midazolam, Temazepam, Flurazepam, and Nitrazepam are indicated for the treatment of insomnia and Lorazepam is considered as a drug having anticonvulsant effects. As the mechanism of action is the same, there should be some differences in the binding patterns with the proteins that create differences in their impacts on the body. A deep screening of the binding patterns of the available Benzodiazepines in the market to the GABA A receptor will be beneficial to find out the responsible amino acids for being accountable for showing any specific action. This reveal will help design new molecules with the highest beneficial effect and lowest toxicity in the body. The in silico method provides the initial level of understanding regarding the binding patterns, performing in vitro and in vivo experiments will be more specific to claim the benefits of newly designed drugs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)