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We commonly use chloral hydrate sedation in newborns, though its cardiorespiratory side effects have not yet been fully investigated. Our study aimed to analyze the impact of chloral hydrate on cardiorespiratory parameters in term newborns. We performed a prospective, pre-post single-arm interventional study in 42 term, respiratorily and hemodynamically stable newborns. Oxygen saturation (SpO2), end-tidal CO2 (ETCO2), the apnea-hypopnea index and the respiratory and heart rates were recorded by polygraphy, starting 0.5-1 hour before oral administration of chloral hydrate at a dose of 40 mg/kg and ceasing 4 hours post-administration. After administration of chloral hydrate, the mean basal SpO2 dropped by 2.0% (from 97.1% to 95.1%; p<0.001) and the mean basal ETCO2 increased by 3.9 mmHg (25.6 to 29.5 mmHg; p<0.001). We found a significant decrease in the minimal SpO2 values (p<0.001) and an increase in the percentage of time spent with SpO2 <95% and <90% (p<0.001). The mean increase in the estimated apnea-hypopnea index was 3.5 events per hour (p<0.001). The mean respiratory and heart rates were significantly lower 150 min after the administration of chloral hydrate when compared with pre-sedation values (51/min and 127/min versus 61/min and 138/min respectively; p<0.001). A considerable number of patients exhibited changes in cardiorespiratory parameters that differed considerably from the normal ranges. In conclusion, SpO2, ETCO2, the estimated apnea-hypopnea index and the respiratory and heart rates changed after the administration of chloral hydrate. They remained within normal limits in most newborns, but the inter-individual variability was high in the studied population. [ABSTRACT FROM AUTHOR]

We conducted a systematic review that examined the link between individual drug categories and violent outcomes. We searched for primary case-control and cohort investigations that reported risk of violence against others among individuals diagnosed with drug use disorders using validated clinical criteria, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We identified 18 studies published during 1990-2019, reporting data from 591,411 individuals with drug use disorders. We reported odds ratios of the violence risk in different categories of drug use disorders compared with those without. We found odds ratios ranging from 0.8 to 25.0 for most individual drug categories, with generally higher odds ratios among individuals with polydrug use disorders. In addition, we explored sources of between-study heterogeneity by subgroup and meta-regression analyses. Cohort investigations reported a lower risk of violence than case-control reports (odds ratio =  2.7 (95% confidence interval (CI): 2.1, 3.5) vs. 6.6 (95% CI: 5.1, 8.6)), and associations were stronger when the outcome was any violence rather than intimate partner violence (odds ratio = 5.7 (95% CI: 3.8, 8.6) vs. 1.7 (95% CI: 1.4, 2.1)), which was consistent with results from the meta-regression. Overall, these findings highlight the potential impact of preventing and treating drug use disorders on reducing violence risk and associated morbidities. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We aimed to estimate incident frailty risks of prescription drugs for pain and for sleep in older US adults. DESIGN: Longitudinal cohort. SETTING: Health and Retirement Study. PARTICIPANTS: Community‐living respondents aged 65 years and older, excluding individuals who received recent treatment for cancer (N = 14 208). Our longitudinal analysis sample included respondents who were not frail at baseline and had at least one follow‐up wave with complete information on both prescription drug use and frailty, or date of death (N = 7201). MEASUREMENTS: Prescription drug use for pain and sleep, sociodemographics, other drug and substance use, and Burden frailty model components. Multivariable drug use stratified hazard models with death as a competing risk evaluated frailty risks associated with co‐use and single use of prescription drugs for pain and for sleep. RESULTS: Proportions endorsing prescription drug use were 22.1% for pain only, 6.8% for sleep only, and 7.7% for both indications. Burden frailty model prevalence was 41.0% and varied significantly by drug use. Among non‐frail individuals at baseline, proportions endorsing prescription drug use were 14.9%, 5.6%, and 2.2% for the three indications. Prescription drug use was associated with increased risk of frailty (co‐use adjusted subhazard ratio [sHR] = 1.95; 95% confidence interval [CI] = 1.6‐2.4; pain only adjusted sHR = 1.58; CI = 1.4‐1.8; sleep‐only adjusted sHR = 1.35; CI = 1.1‐1.6; no use = reference group). Cumulative incidence of frailty over 8 years for the four groups was 60.6%, 50.9%, 45.8%, and 34.1%. Sensitivity analyses controlling for chronic diseases associated with persistent pain resulted in minor risk reductions. CONCLUSION: Prescription pain and sleep drug use is significantly associated with increased incidence of frailty. Research to estimate effects of pain and sleep indications and of drug class–specific dosage and duration on incident frailty is indicated before advocating deprescribing based on these findings. J Am Geriatr Soc 67:2474–2481, 2019 See related editorial by Paula Rochon and related article by Shahar Shmuel [ABSTRACT FROM AUTHOR]

• Our approach, ANMTE, can reach a success rate of 88 % without sedative, which is comparable to those studies using sedation. • ANMTE method not only improved the efficiency and success rate but also guaranteed image quality. • Focusing the potential effective influences of children's mutual learning. To evaluate the benefits of a multifaceted concept, ANMTE (Appropriate Number of children, appropriate learning Methods, appropriate adaptive Training, and appropriate Encouragement), proposed by our group, in improving the success rate, efficiency and image quality of Magnetic Resonance (MR) examinations for children from 3 to 6 years old. In this study, 150 participants were included from July 2019 to January 2023, including 50 non-sedated children in ANMTE group, 50 in the group with sedative, and 50 in the group with routine preparations. ANMTE refers to appropriate number of children, appropriate learning methods, appropriate adaptive training, and appropriate encouragement, developed by our group for MR examinations of children from 3 to 6 years old. Group differences in success rate, efficiency, and image quality were evaluated across the three groups using Kaplan-Meier, Log-rank and Chi-square test, respectively. The rates of successful MR examinations were 44/50 (88 %), 45/50 (90 %), and 36/50 (72 %) for ANMTE group, the group with sedatives and the group with routine preparations, respectively (P = 0.03). Image quality of the 3 groups showed no significant group difference (P = 0.067). In terms of the median duration of MR examinations, ANMTE group was comparable to the group with sedative (both were about 10.0 min), but better than the group with routine preparations (16.5 min) (P = 0.024). We demonstrated the feasibility of our comprehensive nursing method ANMTE in MR examinations of young children, similar to the group with sedative at the success rate and image quality as well as the durations of MR examinations. ANMTE has not only better efficiency but also higher safety as it does not require sedative, which could be promising in clinical routine MR examinations for young children aged 3–6 years old. [ABSTRACT FROM AUTHOR]

Anxiety and insomnia are among the most common mental health disorders and are a major cause of disability around the world. Traditional herbal medicines are receiving significant attention in global health debates. Several Italian regions maintain rural traditions and are among the most extensively studied areas of Europe regarding medicinal plant uses. The present overview aims to highlight the use of wild and cultivated plants, specifically as sedatives and for insomnia treatment in Italy, and to collect, analyze, and summarize the available literature about their pharmacological activity as well as clinical and pre-clinical studies concerning the most cited plants. In total, 106 wild taxa are used in Italy for sedative purposes. The plant species belong to 76 genera and 32 families, of which the most cited are Asteraceae (24.2%) and Lamiaceae (21.1%). Leaves (29%) and flowers (27%) are the plant parts mostly used as infusion (70%) and decoction (25%). Out of 106 taxa documented, only the most cited are analyzed in this overview (A. arvensis L., C. nepeta L., C. monogyna Jacq., H. lupulus L., L. nobilis L., L. angustifolia Mill., M. sylvestris L., M. chamomilla L., M. officinalis L., O. basilicum L., P. rhoeas L., P. somniferum L., R. officinalis L., T. platyphyllus Scop., and V. officinalis L.). Among the fifteen species selected, only seven have been studied for their pharmacological activity as hypnotic-sedatives. Future pre-clinical and clinical studies are needed to better clarify the mechanism of action of bioactive compounds and confirm the potential of these alternative therapies.

Context: In Northern Nigeria, Pavetta crassipes (K. Schum) Rubiaceae leaf extracts are used in the treatment of convulsion, pain and mental illness; however, there is paucity of information on its neuropharmacological effects. Aims: To evaluate the neuropharmacological effects of the aqueous leaf extract and fractions of Pavetta crassipes. Methods: Pavetta crassipes leaves were harvested, dried and powdered using an electric mill. Hot aqueous extraction was done with 250 g powdered leaf in 1000 mL distilled water. The dry extract was partitioned in various solvents with only the aqueous fraction (AF), and butanol fraction (BF) giving significant yields. Neuropharmacological effects including anticonvulsant, behavioural, antipsychotic, muscle relaxant and sedative effects were evaluated in the extract and fractions at doses of 100, 200 and 400 mg/kg, using standard methods. Results: The onset of strychnine induced convulsions was significantly (p

Abstract Background Persicaria hydropiper Linn. (Family: Polygonaceae), it grows in damp places and the bank of rivers, canals, lakes, and roadsides of Bangladesh. The leaves of the plant used in traditional medicine to treat insomnia, depression, and neurodegenerative diseases. The objective of this study is to investigate the sedative and anxiolytic activities of the methanol extract of leaves of Persicaria hydropiper (MEPH). Methods The sedative effect of the P. hydropiper at the doses of 50, 200, 350, and 500 mg/kg evaluated using the open field, hole cross, rota-rod and thiopental sodium-induced sleeping time test in mice. The anxiolytic activity evaluated using the elevated-plus maze, light-dark box, hole-board and marble-burying test. Sedative and anxiolytic activities compared to diazepam, a positive control. The acute toxicity test also assessed. Results The neuropharmacological activity of both open field and hole cross tests significant (p

Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20–50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons.

Background: Optimal use of psychotropic medications for people living with dementia is important. By finding potentially modifiable factors, dementia care teams may find solutions to achieve the appropriate use of psychotropic drugs., Objective: This study aimed to elucidate patient and caregiver factors associated with the use of psychotropic drugs listed in the potentially inappropriate medications (PIMs) in community-dwelling people with dementia., Methods: This cross-sectional study enrolled 808 patients newly diagnosed with dementia, and their caregivers, from a dementia clinic at Changhua Christian Hospital. Patient and caregiver characteristics, care mode, and social resource usage were recorded. Multivariate logistic regression was used to identify factors associated with prescribing psychotropic medications., Results: Of all the participants, 39.1% used at least one of psychotropic medication categorized as PIM. Patients with frontotemporal dementia, with behavior or psychological symptoms, or cared by sole foreign care workers; caregivers with higher depression scores, employed or non-spouse caregivers carried a higher risk of prescription of psychotropic medications listed in PIMs., Conclusion: Psychotropic drug prescriptions are associated with patient and caregiver factors. Therefore, implementing appropriate interventions, especially those targeting potentially modifiable factors, is important to reduce psychotropic medication use., 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., (Copyright © 2024 Chan, Wang, Tung, Chang, Chan and Jhang.)

Background: Ficus benghalensis has been used by local health care practitioners to treat pain, inflammation, rheumatism, and other health issues., Objective: In this study, the crude extract and diverse fractions, along with the isolated compound of F. benghalensis were examined for their roles as muscle relaxants, analgesics, and sedatives., Methods: The extract and isolated compound 1 were screened for muscle-relaxant, analgesic, and sedative actions. The acetic acid-mediated writhing model was utilized for analgesic assessment, the muscle relaxant potential was quantified through traction and inclined plan tests, and the open field test was applied for sedative effects., Results: The extract/fractions (25, 50, and 100 mg/kg) and isolated compounds (2.5, 5, 10, and 20 mg/kg) were tested at various doses. A profound (p< 0.001) reduce in the acetic acid-mediated writhing model was observed against carpachromene (64.44%), followed by ethyl acetate (60.67%) and methanol (58.42%) fractions. A marked (p< 0.001) muscle relaxant activity was noticed against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Regarding the sedative effect, a significant action was noted against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Furthermore, the binding modes of the isolated compounds were explored using molecular docking. The molecular docking study revealed that the isolated compound possessed good binding affinity for COX2 and GABA. Our isolated compound may possess inhibitory activity against COX2 and GABA receptors., Conclusion: The extract and isolated compounds of Ficus benghalensis can be used as analgesics, muscle relaxants, and sedatives. However, detailed molecular and functional analyses are essential to ascertain their function as muscle relaxants, analgesics, and sedatives.

Introduction: Ziziphus mauritiana , sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have analgesic, antipyretic, potent analgesic, anti-inflammatory, and anti-emetic properties., Aims & Objectives: The aim of this study is to investigate the sedative and anticonvulsant activities of Ziziphus mauritiana extract by governing 200 and 400 mg/kg body weight orally., Materials and Methods: The leaves are extracted with ethanol and lukewarm water with a soxhlet apparatus for 72 hours. After that acute extract toxicity study was performed and then locomotor activity, pentobarbital induced sleeping time and anticonvulsant activity were performed with the extract., Results: Oral administration of extract at dosages of 200 & 400 mg/kg was employed after an immediate toxicity test. At a dosage of 400 mg/kg, the number of locomotions was reduced significantly lengthened the period of time spent sleeping and there was showed a dosage-dependent reduction in all phases of an epileptic episode., Conclusion: In this study, the extract reduced locomotor activity, however, it had a superior profile for an antiepileptic action than phenytoin since it decreased locomotor activity to a lesser level. The considerable increase in pentobarbitone sleep hours with the extracts at a higher dose supported the sedative action of Z. mauritiana ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.

Midazolam is a benzodiazepine with sedative, muscle relaxant, anxiolytic, and anticonvulsant effects. Twelve ball pythons (Python regius) were used in a parallel study evaluating the pharmacokinetics of 1 mg/kg midazolam following a single intracardiac (IC) or intramuscular (IM) administration. Blood was collected from a central venous catheter placed 7 days prior, or by cardiocentesis, at 15 time points starting just prior to and up to 72 hr after drug administration. Plasma concentrations of midazolam and 1‐hydroxymidazolam were determined by the use of high‐performance liquid chromatography tandem‐mass spectrometry and pharmacokinetic parameters were estimated using noncompartmental analysis. The mean ± SD terminal half‐lives of IC and IM midazolam were 12.04 ± 3.25 hr and 16.54 ± 7.10 hr, respectively. The area under the concentration‐time curve extrapolated to infinity, clearance, and apparent volume of distribution in steady‐state of IC midazolam were 19,112.3 ± 3,095.9 ng*hr/ml, 0.053 ± 0.008 L hr−1 kg−1, and 0.865 ± 0.289 L/kg, respectively. The bioavailability of IM midazolam was estimated at 89%. Maximum plasma concentrations following an IM administration were reached 2.33 ± 0.98 hr and 24.00 ± 14.12 hr postinjection for midazolam and 1‐hydroxymidazolam, respectively, and 22.33 ± 20.26 hr postinjection for 1‐hydroxymidazolam following IC administration. [ABSTRACT FROM AUTHOR]

To evaluate the effects of midazolam and nitrous oxide (N 2 O) on the minimum anesthetic concentration of isoflurane (MAC ISO) in ball pythons. Prospective, crossover, randomized, semi-blinded study. A total of nine healthy adult female ball pythons (Python regius) weighing 2.76 ± 0.73 kg. In each snake, three protocols were evaluated with 2 week washouts: treatment MID–O 2 , midazolam (1 mg kg−1) administered intramuscularly (IM) and anesthesia induced with isoflurane–oxygen; treatment SAL–O 2 , saline (0.2 mL kg−1) IM and anesthesia with isoflurane–oxygen; and treatment SAL–N 2 O, saline IM and anesthesia with isoflurane and 50% nitrous oxide (N 2 O):50% oxygen. In each treatment, isoflurane was administered by face mask immediately after premedication. Snakes were endotracheally intubated and inspired and end-tidal isoflurane concentrations were monitored. The study design followed a standard bracketing technique, and the MAC ISO was determined using logistic regression. Electrical stimulation using a Grass stimulator connected to the base of the tail (50 V, 50 Hz, 6.5 ms pulse−1) was used as the supramaximal stimulus. Blood-gas analysis was performed on cardiac blood collected immediately following intubation and after the last stimulation. Blood-gas variables were compared over time and between treatments using linear mixed models. MAC ISO at a body temperature of 30.1 ± 0.4 °C was 1.11% (95% confidence interval, 0.94–1.28%) in SAL–O 2 and was significantly decreased to 0.48% (0.29–0.67%) in MID–O 2 (p < 0.001) and to 0.92% (0.74–1.09%) in SAL–N 2 O (p = 0.016). PO 2 was significantly lower in MID–O 2 and SAL–N 2 O than in SAL–O 2. Midazolam significantly decreased the MAC ISO by 57% in ball pythons, whereas addition of N 2 O resulted in a modest, although significant, decrease (17%). MAC ISO in ball pythons was lower than those previously reported in reptiles. [ABSTRACT FROM AUTHOR]

Experimental based evidence suggests that most of the medicinal plants possess wide-ranging pharmacological and biological activities that may possibly use in treatment of inflammation-related diseases. The current study was aimed to explore the acute toxicity, analgesic, sedative and antipyretic activities of Monotheca buxifolia and Bosea amherstiana in mices. In vivo experimental models were used in this study. Acute toxicity was evaluated for 24 h' interval at concentration of 500, 1000, 1500 and 2000 mg/kg. The analgesic activity was estimated by acetic acid induced writhing test. White wood apparatus enclosed in stainless steel was used for sedative experiment and antipyretic activity was evaluated in brewer's yeast induced hyperthermic at 50, 100 and 150 mg/kg i.p. Both plants were found safe at all tested doses. Monotheca buxifolia and Bosea amherstiana dose-dependently reduced abdominal constrictions in mice. Both plants exhibited significant (P < 0.0001) sedative effects in dose of 50, 150 and 150 mg/kg. Both plants markedly (P < 0.0001) reduced yeast induced hyperthermia. The inhibitions were dose-dependent and remained significant up to five hours of administration. These investigational results have linked a pharmacological indication for the traditional claim of the drugs to be used as an anti-inflammatory, analgesics and antipyretic agents. [ABSTRACT FROM AUTHOR]

Background: Older adult prescription tranquilizer/sedative misuse is understudied, despite evidence of increased misuse prevalence and significant associated consequences (e.g., suicidal ideation). Identification of misuse sources could limit such misuse by offering policymakers and clinicians targets to limit diverted tranquilizer/sedative medication. Objective: To establish the prevalence of tranquilizer/sedative misuse sources in older adults and investigate associated poor outcomes. Methods: Data were from the 2009–14 National Survey on Drug Use and Health, including participants endorsing one or more past-month tranquilizer/sedative misuse sources (n = 3,162) with older adult (50–64 and 65 and older; n =160) tranquilizer/sedative source prevalence estimated and compared to younger cohorts. Results: Adults 65 and older had the greatest physician source use (38.2%) across ages. Physician source use in those 50 and older, relative to those obtaining medication from friends/family for free, was linked to a higher prevalence of both past-year prescription opioid misuse (58.6% versus 34.9%) and serious psychological distress (50.1% versus 11.6%). Conclusions/Importance: Physician source use is particularly prevalent in adults 65 and older, and adults 50 and older using physician sources appear at elevated risk of consequences. Careful monitoring of psychiatric symptoms in older adults receiving tranquilizers/sedatives appears warranted. Older adults use a unique pattern of tranquilizer/sedative misuse sources, as compared to younger groups, further signaling that older adult misuse processes differ from those in younger groups. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the association between the use of various sedative-hypnotics and the incidence of overall and individual cancers in a large, population-based, retrospective cohort study.Methods: We selected a 5% random sample of individuals aged 50 years or older from data maintained by the Korean National Health Insurance Service for the years 2002-2015, excluding individuals with a prior diagnosis of cancer and with any sedative-hypnotic use in the initial two years of follow-up, leaving 236,759 participants for the final analysis. Exposure to sedative-hypnotics was defined by type of drug, standardized to a defined daily dose, and coded as a time-varying variable. Cox proportional hazard models were applied after adjusting for sex, socio-economic status, and comorbidities.Results: We observed increased risk for overall cancer among men and women who used sedative-hypnotics (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.01-1.13 for men; HR = 1.21, 95% CI = 1.09-1.25 for women) compared with non-users after full adjustment. In the fully adjusted model, women with any sedative-hypnotic use had significantly increased risk for thyroid (HR = 1.53, 95% CI = 1.24-1.87), breast (HR = 1.29, 95% CI = 1.04-1.61), ovarian (HR = 1.65, 95% CI = 1.10-2.46), and lung cancer (HR = 1.40, 95% CI = 1.17-1.69) compared with non-users. Men with sedative-hypnotic use had increased risk for prostate (HR = 1.36, 95% CI = 1.16-1.58), brain (HR = 1.67, 95% CI = 1.04-2.69), and lung cancer (HR = 1.20, 95% CI = 1.07-1.35) compared with non-users.Conclusion: We found a significant increase in overall cancer incidence among participants who used sedative-hypnotics, and both male and female sedative-hypnotic users had significantly increased risk for certain types of cancer. [ABSTRACT FROM AUTHOR]

Impacts of pre-sampling practices on fish plasma biochemistry may bias the outcome of a study if not considered within the general sampling strategy. Acute handling stresses can be imposed on fish during capture, and it is common practice to immobilise fish via sedation prior to obtaining blood samples for non-lethal extraction purposes, and/or to reduce stress, pain, or suffering before being euthanised. We investigated these potential influences using a Chinook salmon model (Oncorhynchus tshawytscha) by measuring levels of 119 biochemical targets comprising ions, metabolites, and enzymes in plasma. Multivariate analyses showed that 2 min of confinement with mild handling manipulation led to a significant departure from baseline metabolism, which was further exasperated during a prolonged 5-min challenge. These changes were characterised by a disruption in osmoregulation, a switch towards anaerobic metabolism, and shifts in ammonia recycling, among others. Sedation of fish with clove oil and AQUI-S® had major impacts on plasma biochemical profiles, with alterations signalling changes in glycolytic metabolism, respiratory modes, carbon flux through the TCA cycle, and lipid compartmentalisation. Sedation also enhanced levels of plasma amino acids, revealing a key difference between responses to handling stress and sedation. These results demonstrate that pre-harvest practices should be carefully managed during fish sampling for biochemical/metabolomic-based analyses, and if manipulations are essential, they should be standardised. [ABSTRACT FROM AUTHOR]

Purpose: Postintubation hypotension (PIH) is an adverse event associated with poor outcomes in emergency department (ED) endotracheal intubation. This study aimed to evaluate the association between sedative dose adjustment and PIH during emergency airway management. We also investigated the impact of patient and procedural factors on the incidence of PIH.Materials and Methods: This was a single-center, retrospective study that used a prospectively collected registry of airway management performed at the ED from April 2014 to February 2017. Adult patients who received emergency endotracheal intubation were included. Multivariable logistic regression models were used to evaluate the association of PIH with sedative dose, patient variables, and procedural variables.Results: Overall, 689 patients were included, and 233 (33.8%) patients developed PIH. In the patients overall, multivariable logistic regression demonstrated that age > 70 years, shock index >0.8, arterial acidosis (pH < 7.2), intubation indication, and use of non-depolarizing neuromuscular blocking agent were significantly related to PIH. In patients overall, the sedative dose was not related to PIH (overdose; OR: 1.09, 95%CI: 0.57-2.06), (reduction; OR: 0.93, 95%CI: 0.61-1.42), (none used; OR: 1.28, 95%CI: 0.64-2.53). In subgroup analysis, ketamine dose was not related to PIH (overdose; OR: 0.81, 95%CI: 0.27-2.38, reduction; OR: 1.41, 95%CI: 0.78-2.54). Reduction of etomidate dose was significantly associated with decreased PIH (reduction; OR: 0.46, 95%CI: 0.22-0.98, overdose; OR: 1.77, 95%CI: 0.79-3.93).Conclusions: PIH was mainly related to predisposing patient-related factors. Only adjustment of etomidate dose was associated with the incidence of PIH. [ABSTRACT FROM AUTHOR]

Background: Drug Burden Index (DBI), a measure of exposure to medications with anticholinergic and sedative activity, has been associated with poorer physical function in older adults in the general population. While extensive study has been conducted on associations between DBI and physical function in older adults in the general population, little is known about associations in older adults with intellectual disabilities (ID). This is the first study which aims to examine the association between DBI score and its two sub-scores, anticholinergic and sedative burden, with two objective measures of physical performance, grip strength and timed up and go, and a measure of dependency, Barthel Index activities of daily living, in older adults with ID.Methods: Data from Wave 2 (2013/2014) of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) was analysed. Analysis of Covariance (ANCOVA) was used to detect associations and produce adjusted means for the physical function and dependency measures with respect to categorical DBI scores and the anticholinergic and sedative sub-scores (DBA and DBS).Results: After adjusting for confounders (age, level of ID, history of falls, comorbidities and number of non-DBI medications, Down syndrome (grip strength only) and gender (timed up and go and Barthel Index)), neither grip strength nor timed up and go were significantly associated with DBI, DBA or DBS score > 0 (p > 0.05). Higher dependency in Barthel Index was associated with DBS exposure (p < 0.001).Conclusions: DBI, DBA or DBS scores were not significantly associated with grip strength or timed up and go. This could be as a result of established limitations in physical function in this cohort, long-term exposure to these types of medications or lifelong sedentary lifestyles. Higher dependency in Barthel Index activities of daily living was associated with sedative drug burden, which is an area which can be examined further for review. [ABSTRACT FROM AUTHOR]

Corni fructus, the fruit of Cornus officinalis Sieb. et Zucc., has been used as a tonic for the kidney in China for thousands of years. Loganin is one of the major constituents derived from Corni fructus. In this study, we revealed the sedative and hypnotic activity of loganin and investigated its mechanisms for the first time. Pentobarbital-induced sleep test and insomnia mice models [induced by caffeine and p-chlorophenylalanine (PCPA)] were used for the assessment of sedative and hypnotic effects of loganin. It was found that loganin (20–50 mg/kg) exerted sedative effect in normal mice. Loganin exhibited hypnotic effect by increasing sleep onset and sleep duration in pentobarbital-treated mice, recovering PCPA-induced insomnia and exerting synergistic hypnosis effect with 5-HTP. In addition, electroencephalograph (EEG) and electromyography (EMG) recordings of rats showed that loganin (35 mg/kg) prolonged the ratio of non-rapid eye movement (NREM) sleep and shortened wakefulness significantly, further immunohistochemistry showed that loganin (35 mg/kg) increased c-Fos expression in GABAergic neurons of rats in the ventrolateral preoptic nucleus (VLPO). The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite were measured in the hippocampus, prefrontal cortex and striatum of mice, 1 h after loganin (35 mg/kg) treatment. 5-HT, 5-HIAA/5-HT, DA, and DOPAC were decreased significantly in the prefrontal cortex. In conclusion, these results indicated that loganin produced beneficial sedative and hypnotic activity, which might be mainly mediated by modification of the serotonergic system and GABAergic neurons. [ABSTRACT FROM AUTHOR]

Thai traditional antinausea remedy is drug registered in the National List of Essential Medicines for the treatment of blood circulation disorders, dizziness, fatigue, and insomnia. Antinausea remedies have long been used, but their effects and action mechanisms remain poorly understood. Here, hypnotic, sedative, and anxiolytic activities of antinausea remedies were evaluated. This preclinical trial assessed the hypnotic, sedative, and anxiolytic activities of antinausea remedies. Thai traditional antinausea remedy was extracted by decoction in deionized water until exhaustion and concentrated to dryness. Anxiolytic activities were evaluated using elevated plus-maze and open-field tests for vehicle control group compared to treatment groups (50, 100, and 200 mg/kg). Hypnotic and mechanistic studies were performed using thiopental sodium-induced sleeping time with benzodiazepine receptor antagonist test. In the thiopental sodium-induced sleeping time test, vehicle control groups were compared to treatment groups (10, 50, and 100 mg/kg). In addition, GABAergic agonistic effect vehicle control groups were pretreated with 3.5-mg/kg flumazenil before sterile water and compared to the treatment group which also received flumazenil before 100 mg/kg extract. Data were statistically analyzed using analysis of variance followed by multiple comparison testing. The aqueous extract was found to be a hypnotic and sedative agent with a dose response either as latent period or prolonged sleeping time (P < 0.05) and a successive GABAergic agonistic effect. Locomotor determination revealed the tendency to relieve anxiety. Thai traditional antinausea remedy can induce sleep and be safely used to reduce anxiety. [ABSTRACT FROM AUTHOR]

Little has been published regarding intravenous (IV) ketamine for burn wound care in adult patients. Ketamine may serve as a safe alternative to provide conscious sedation and limit opioid administration to patients. The purpose of this study was to characterize IV ketamine use during burn wound care and establish its potential role as a safe adjunct to opioid and benzodiazepine medications. This is a retrospective review of adult patients admitted to a regional burn center who received IV ketamine for burn wound care. Patient demographics, medications, and ketamine-related adverse effects including hypertension and dysphoric reactions were recorded. Cardiopulmonary complications were also tracked. Thirty-six patients met inclusion criteria; fifty total cases were performed. The median patient age was 37 (interquartile range [IQR]: 28-55] years with a median burn size of 9.5 (IQR: 4.0-52) %TBSA. The median ketamine dose administered was 1.2 (IQR: 0.8-2.1) mg/kg. IV midazolam was administered in almost all cases (98%) at a median dose of 3.0 (IQR: 2.0-5.0) mg. Opioids were administered in 13 of 50 cases (26%) at a median morphine equivalent dose of 10 (IQR: 5.0-18) mg. In 46 cases (92%), patients denied unpleasant recall of medication. Dysphoric reactions were observed in three cases (6%). Ketamine-induced hypertension occurred in three cases (6%) and all immediately responded to IV labetalol. There were no cardiopulmonary complications. These findings suggest that IV ketamine provides a safe analgesia and sedative option for burn wound care. Given these findings, IV ketamine for burn wound care warrants further study. [ABSTRACT FROM AUTHOR]

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BACKGROUND: During the MRI examination, pediatric patients sleep under the sedation so that the image artifacts caused by the patient motion could be minimized. However, the sedative injection at the buttocks might cause a difficulty in the diagnosis of the buttock diseases using the MRI manifestations. OBJECTIVE: This study aims to explore the imaging characteristics of MR for the pediatric patients with the sedative injected at the buttocks in order to correctly diagnose the diseases. METHODS: MR imaging data of 64 pediatric patients injected with the sedative at the buttocks were retrospectively collected, including 8 cases of buttock disease. The imaging manifestations were analyzed and compared. RESULTS: Out of 64 patients, 8 were diagnosed as the buttock diseases. MR imaging manifestations of the sedatives injected at the buttocks were the locally patchy and streaky long T1 and long T2 signals and were different from what were shown for the normal tissues and diseases. CONCLUSION: The sedative injected at the buttocks has the MRI manifestations different from the normal tissues and diseases. Correctly understanding the MRI manifestations for the pediatric patients with the injection of sedative at the buttocks would reduce the chances of the misdiagnosis on the diseases. [ABSTRACT FROM AUTHOR]

The study is conducted to observe and investigate the effects of oral dosing of methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) on neuropharmacological activities of mice. Methanolic extracts of Cuminum nigrum (L) and Centratherum anthelminticum (L) were soluble in Dimethyl sulphoxide (DMSO) i.e. an organic solvent, so it is used in this study. Screening for anxiolytic and antidepressant effects were performed using open field test, head dip test, stationary rod test, cage crossing test, light and dark box and swimming- induced depression test. Thirty animals were divided into three groups of 10 animals each and numbered as 1 (control, on DMSO), 2(on methanolic extract of Cuminum nigrum (L), 3 (on methanolic extract of Centratherum anthelminticum (L). The extracts and DMSO were administered orally for 60 days. Any possible change in animal behavior was evaluated on day 15, 30 and 60 of dosing. The groups 2 and 3 showed significant increase (p<0.001, p<0.01) in open field activity and light and dark box test respectively, while significantly decreased activity was observed in head dip and cage crossing activity (p<0.01) after 60 days of dosing. Based on above findings, it is suggested that the extracts of Centratherum anthelminticum (L) and Cuminum nigrum (L) have antidepressant and anxiolytic potential with sedative effects. [ABSTRACT FROM AUTHOR]

The sedative effects of the essential oil released by living Ocimum basilicum (basil) plants were investigated using a mouse activity monitoring system. Ocimum basilicum plants were grown in a hydroponic chamber, and either the headspace air from the hydroponic chamber or the essential oil extracted from mature plants was administered by the inhalation route to mice in an open field test. The most effective dose of O. basilicum essential oil for reducing the locomotor activity of the mice was found to be 4.0 × 10−3 mg per cage. The headspace air was administered to mice held in a glass cage via a Teflon tube connected to a hydroponic chamber containing O. basilicum plants. A significant decrease in locomotor activity was observed when the hydroponic chamber contained nine plants. The results of this study demonstrate that the headspace air of living basil plants could effectively reduce the locomotor activity of mice. [ABSTRACT FROM AUTHOR]

Background: Prescription tranquilizer/sedative (e.g., alprazolam, zolpidem) misuse (i.e., use in ways not intended by the prescriber or without a prescription) is understudied, with little research identifying misuse correlates. Identification of key correlates could identify subgroups more likely to engage in misuse, allowing for targeted treatment. This work examines tranquilizer/sedative use and misuse prevalence rates and misuse correlates across U.S. age cohorts, using nationally representative data.Methods: Data were from the 2015-16 National Survey on Drug Use and Health (n = 114,043). Analyses used design-based logistic regression for past-year tranquilizer/sedative misuse correlates across participants or those engaged in past-year use; past-month misuse correlates were also examined in those with past-year misuse.Results: Young adults (18-25 years) had the highest prevalence of past-year and past-month tranquilizer/sedative misuse, with 42.8% of those with past-year use also engaged in misuse. Mental health correlates were associated with past-year misuse, while substance use, particularly opioid misuse, was associated with both past-year and past-month misuse. Substance use correlate strength was most likely to vary by age group, with older adults (65 years and older) having fewer significant correlates overall.Conclusions: This work highlighted young adults and those with other substance use as most likely to engage in tranquilizer/sedative misuse. In particular, those endorsing suicidality and reporting opioid misuse are a subgroup of concern, given their especially elevated rates of misuse and the increased risk for overdose imparted by tranquilizer/sedative medication. Workplace-based interventions for young adults and school-based universal prevention may be warranted to limit tranquilizer/sedative misuse in these groups. [ABSTRACT FROM AUTHOR]

In this article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives 1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant, sedative activity and neurotoxicity using the maximal electroshock (MES) model, sc-pentylenetetrazol (PTZ) model, pentobarbital sodium-induced sleeping model, and locomotor activity tests, respectively. Among them, compounds 4, 9 and 16 exhibited good anticonvulsant activity in primary evaluation. Furthermore, compound 4 is the most effective anticonvulsant and sedative agent in subsequent tests, while the low threshold of toxicity of compound 4 is vigilant. Compounds 9 and 16 also performed significantly anticonvulsant activity in subsequent tests with weak toxicity. The molecular modeling experiments also predicted good binding interactions of the obtained active molecules with the GABA transferas. Therefore, it could be concluded that the synthesized derivatives 4, 9 and 16 would represent useful lead compounds for further investigation in the development of anticonvulsant and sedative agents. [ABSTRACT FROM AUTHOR]

Chukrasia velutina is a local medicinal plant commonly known as chikrassy in Bangladesh, India, China, and other South Asian countries. The leaves, bark, and seeds are vastly used as herbal medicine for fever and diarrhea, and its leaves essential oils are used for antimicrobial purposes. In this study, we discuss the neuropsychiatric properties of C. velutina leaves through several animal models, quantitative and qualitative phytochemical analysis, and computational approaches. Neuropsychiatric effects were performed in rodents on the methanolic extract of C. velutina leaves (MECVL). Antidepressant, anxiolytic, and sedative effects experimented through these rodent models were used such as the force swimming test (FST), tail suspension test (TST), hole board test (HBT), elevated plus maze test (EPMT), light/dark box test (LDBT), open field test (OFT), and hole cross test (HCT). In these rodent models, 200 and 400 mg/kg doses were used which exhibited a significant result in the force swimming and tail suspension test (p < 0.001) for the antidepressant effect. In the anxiolytic study, the results were significant in the hole board, elevated plus maze, and light/dark box test (p < 0.001) for doses of 200 and 400 mg/kg. The result was also significant in the open field and hole cross test (p < 0.001) for sedative action in the sake of similar doses. Moreover, qualitative and quantitative studies were also performed through phytochemical screening and GC-MS analysis, and fifty-seven phytochemical compounds were found. These compounds were analyzed for pharmacokinetics properties using the SwissADME tool and from them, thirty-five compounds were considered for the molecular docking analysis. These phytoconstituents were docking against the human serotonin receptor, potassium channel receptor, and crystal structure of human beta-receptor, where eight of the compounds showed a good binding affinity towards the respective receptors considered to the reference standard drugs. After all of these analyses, it can be said that the secondary metabolite of C. velutina leaves (MECVL) could be a good source for inhibiting the neuropsychiatric disorders which were found on animal models as well as in computational studies.

Remimazolam is a newer drug in the field of anaesthesia. It combines the properties of midazolam and remifentanil. As the name indicates, midazolam is the parent compound of remimazolam which incorporates the pharmacokinetic properties of remifentanil. Remimazolam is an ultra short acting anaesthetic agent/sedative which rapidly shows its effect after injection and also wears off expeditiously after cessation. Therefore, remimazolam’s dosage can be ideally controlled. Since it acts on benzodiazepine receptors, availability of specific antagonist (flumazenil) further adds to its safety in case of overdose.