Synthesis of Sedative-hypnotic Zopiclone Analogues

Eight new cyclopyrrolone compounds were synthesized according to the structure activity relationship and action mechanism of Zopiclone, a cyclopyrrolone hypnotic. Their preliminary pharmacodynamics are under investigation.

Sedative and Hypnotic Effects of Tartary Buckwheat Ethanol Extract

[Objective]The aim was to study the sedative and hypnotic effects of Tartary Buckwheat ethanol extract and lay a foundation for further expanding the application of Tartary Buckwheat. [Method]The effects of Tartary Buckwheat ethanol extract on pentobarbital sodium and mice spontaneous action times were recorded. [Result]Ethanol extract of Tartary Buckwheat could prolong mice sleep duration caused by pentobarbital sodium （suprathreshold dosage）,increase mice sleep number caused by pentobarbital sodium （subthreshold dosage）,and obviously inhibit mice spontaneous action times. [Conclusion]Ethanol extract of Tartary Buckwheat has a function of sedation.

Listening to Turkish classical music decreases patients’anxiety,pain,dissatisfaction and the dose of sedative and analgesic drugs during colonoscopy:A prospective randomized controlled trial

AIM： To determine whether listening to music decreases the requirement for dosages of sedative drugs, patients＇ anxiety, pain and dissatisfaction feelings during colonoscopy and makes the procedure more comfortable and acceptable. METHODS： Patients undergoing elective colonoscopy between October 2005 and February 2006 were randomized into either listening to music （Group 1, n = 30） or not listening to music （Group 2, n = 30）. Anxiolytic and analgesic drugs （intravenous midazolam and meperidine） were given according to the patients＇ demand. Administered medications were monitored. We determined their levels of anxiety using the State-Trait Anxiety Inventory Test form. Patients＇ satisfaction, pain, and willingness to undergo a repeated procedure were self-assessed using a visual analog scale. RESULTS： The mean dose of sedative and analgesic drugs used in group 1 （midazolam： 2.1 ± 1.4, meperidine： 18.1 ± 11.7） was smaller than group 2 （midazolam： 2.4 ± 1.0, meperidine： 20.6 ± 11.5）, but without a significant difference （P 〉 0.05）. The mean anxiety level in group 1 was lower than group 2 （36.7 ± 2.2 vs 251.0 ± 1.9, P 〈 0.001）. The mean satisfaction score was higher in group 1 compared to group 2 （87.8 ± 3.1 vs 58.1 ± 3.4, P 〈 0.001）. The mean pain score in group i was lower than group 2 （74.1 ± 4.7 vs 39.0 ± 3.9, P 〈 0.001）. CONCLUSION： Listening to music during colonoscopy helps reduce the dose of sedative medications, as well as patients＇ anxiety, pain, dissatisfaction during the procedure. Therefore, we believe that listening to music can play an adjunctive role to sedation in colonoscopy. It is a simple, inexpensive way to improve patients＇ comfort during the procedure.

Propofol vs traditional sedative agents for endoscopic retrograde cholangiopancreatography:A meta-analysis

AIM:To investigate the efficacy and safety of propofol sedation for endoscopic retrograde cholangiopancreatography(ERCP).METHODS:Databases including PubMed,Embase,and the Cochrane Central Register of Controlled Trials updated as of October 2010 were searched.Main outcome measures were ERCP procedure duration,recovery time,incidence of hypotension and hypoxia.RESULTS:Six trials with a total of 663 patients were included.The pooled mean difference in ERCP procedure duration between the propofol and traditional sedative agents was-8.05(95%CI:-16.74 to 0.63),with no significant difference between the groups.Thepooled mean difference in the recovery time was-18.69(95%CI:-25.44 to-11.93),which showed a significant reduction with use of propofol sedation.Compared with traditional sedative agents,the pooled OR with propofol sedation for ERCP causing hypotension or hypoxia was 1.69(95%CI:0.82-3.50)and 0.90(95%CI:0.55-1.49),respectively,which indicated no significant difference between the groups.CONCLUSION:Propofol sedation during ERCP leads to shorter recovery time without an increase of cardiopulmonary side effects.Propofol sedation can provide adequate sedation during ERCP.

In vivo sedative and muscle relaxants activity of Diospyros lotus L

Objective: To evaluate the sedative effect of Diospyros lotus L(D. lotus) extract in mice using the open field and Rota rod tests.Methods: For the sedative and muscle relaxants activities of extract/fractions of the plant, invivo open field and phenobarbitone-induced sleeping time were used, while the Roda rod test was employed in animals for the assessment of muscle relaxant activity.Results: Results from this investigation revealed that the extracts of D. lotus have exhibited significant sedative effect in mice(45.98%) at 100 mg/kg i.p. When the extract was partitioned with different solvents, the n-hexane fraction was inactive whereas the chloroform fraction was the most active with 82.67% sedative effect at 50 and 100 mg/kg i.p. On the other hand,the ethyl acetate and n-butanol fractions displayed significant sedative effects(55.65% and40.87%, respectively) at 100 mg/kg i.p. Among the tested extract/fractions, only chloroform and ethyl acetate fractions showed significant(P < 0.05) muscle relaxant activity in the Rota rod test.Conclusions: In short, our study provided scientific background to the traditional uses of D.lotus as sedative.

Sedative effects of peanut (Arachis hypogaea L.) leaf aqueous extracts on brain ATP, AMP, Adenosine and Glutamate/GABA of rats

Peanut (Arachis hypogaea L.) leaf aqueous extracts (PLAE) has been reputed to be a type of sleep-aid in China. To investigate the sedative effects and effect pathways of PLAE, rats (n = 31) were employed in two experiments and intragastrically administrated of (1) distilled water, PLAE (500 mg/kg body weight (BW)) and peanut stem aqueous extracts (PSAE, 500 mg/kg BW);(2) 0, 100 or 500 mg/kg BW of PLAE, respectively for at least 14 days. Six relevant neurotransmitters were measured finally. Experiment-1 (n = 16) results showed that the brain Lactate were significantly elevated (p < 0.05) in rat cerebrums after PLAE administrations, compared with Control and PSAE groups. In respect of brain energy system, significant degradations of the brain adenosine triphos- phate (ATP) (p < 0.05) were observed in the brainstems and even the whole brains of rats though PLAE treatments. Moreover, we found that the brain Adenosine monophosphate (AMP) were clearly decreased (p < 0.05) in rat cerebrum and brainstem regions, while the brain Adenosine revealed an increasing propensity (p = 0.076) in the cerebrums of freely behaving rats. After experiment-2 (n = 15), the γ-aminobutyric acid (GABA) concentrations were statistically (p < 0.05) enhanced and the ratios of Glutamate/GABA were simultaneously reduced (p < 0.05) in rat brainstems, no matter which one dose (100 or 500 mg/kg BW) of PLAE were used. Results indicated that PLAE could influence the target neurotransmitters that related to rat circadian rhythms in the specific brain regions, possessing the potentialities as a sedative or sleep-aid for hypnic therapy purposes.

Evaluation of Acute Toxicity and Sedative Effects of Ethylic Extract of <i>Thymelaea lythroides</i>in Wistar Rats

The purpose of this study was to evaluate the acute toxicity and sedative effect of the ethylic extract of Thymelaea lythroides (Tl) on Wistar rats. The study was based on the gavage administration of the ethylic extract of Tl with different doses (i.e. 200, 400, 500 and 5000 mg/kg), where the toxicity and the sedative activity of the plant were observed and the obtained results were analyzed using the ANOVA test followed by the Bonferroni test. The main results of this study showed that the lethal dose of the ethylic extract of Tl was higher than the 5000 mg/kg dose. Moreover, when compared to the control rats, the animals treated with 5000 mg/kg of the extract exhibited significant reduction in appetite for food and water in the first week. Furthermore, results of the psychotropic test conducted during this study showed visible effects on the exploratory activity of the rats. The dose of 5000 mg/kg was also found to have a significant central nervous system effect;the locomotor activities of the animals decreased in a manner similar to those administered with Zepam as control.

Clinical Efficacy of Sedative Cataplasm for Insomnia Patients with Sub-health

[Objectives]This study aimed to observe the clinical efficacy of sedative cataplasm in the treatment of insomnia patients with sub-health.[Methods]A total of 90 insomnia patients with sub-health were randomly and evenly divided into treatment group and control group.The patients in the control group were given Bozi Yangxin pills orally,and those in the treatment group were treated with sedative cataplasm on Shenjue acupoint.The treatment duration was 4 weeks.The Pittsburgh Sleep Quality Index(PSQI)was used to evaluate clinical efficacy.[Results]The overall efficacy of the treatment group and control group was 91.1%and 77.1%,respectively,and the difference between the two was significant(P<0.05).After treatment,the PSQI scores of each group changed significantly(P<0.05).[Conclusions]Sedative cataplasm has a good clinical efficacy on sub-healthy insomnia patients.

Anticonvulsant, Sedative and Antidepressant Effects of Aqueous Extract of Costus afer Stems in Mice

Epilepsy is a disorder in the nervous system which often causes a loss of consciousness. Traditional treatments are quiet a component of health care system in various populations in spite of the fact that well-established options are available. Most plants are used to treat epilepsy or those which have been verified for anticonvulsant activity were reported. Then, Costus afer is a plant of the Congolese flora used in traditional medicine for its many virtues. Therefore, the anticonvulsant activity of Costus afer was assessed with the strychnine convulsion induction test. Two tests were used for sedative activity such as the barbiturate sleep induction test and motor activity and finally the forced swimming test was also used to assess antidepressant activity. The results showed that the aqueous extract of Costus afer stems had no effects on strychnine-induced seizures at doses of 250 mg/kg and 500 mg/kg compared to the control group. However, the extract of Costus afer stems caused a very significant decrease in motricity at a dose of 500 mg/kg, showing a decrease in the onset time and a very significant increase in sleep duration like the reference molecule such as Diazepam. The aqueous extract of Costus afer stems also caused a decrease in immobility time in mice at a dose of 500 mg/kg.

Evaluation of Anxiolytic and Sedative-Like Activities of Methanolic Extract of <i>Euphorbia hirta</i>Leaves in Mice

In indigenous or folk medicine, Euphorbia hirta is a very popular herb and used as a palliative to treat various ailments including intestinal parasites, diarrhoea, vomiting, amoebic dysentery, asthma, bronchitis, emphysema, coughs, kidney stones, menstrual problems etc. The objective of this study is to evaluate the anxiolytic and sedative-like effects of the methanol extract from the leaves of Euphorbia hirta (Euphorbiaceae). Methanolic extract of Euphorbia hirta was evaluated for its CNS depression effect using mice behavioral models such as, elevated plus maze and hole board test for its anxiolytic potential where hole cross and pentobarbital-induced sleeping time tests were performed for its sedative properties, respectively. The test group received three different doses of the MEHL (100 mg/kg, 200 mg/kg and 300 mg/kg) orally. The positive control group received diazepam (1 mg/kg) orally where the negative control group received distilled water (10 ml/kg) orally. In elevated plus maze test, the extract exhibited significant (p d the number of open arm entry and time spent in open arm by mice compared to control group. In addition, the number of head dips and hole crosses significantly (p < 0.05) decreased by mice in hole board and hole cross tests respectively, compared to control group. Moreover, mice treated with MEHL significantly decrease the onset of sleep and increase the duration of sleep in pentobarbital-induced sleeping time test in mice compared to control group. The data obtained from the present study clearly demonstrate that the methanolic extract of Euphorbia hirta has potential anxiolytic and sedative-like activity in the animal behavioral models. And the findings represent a rational explanation for its use in traditional medicine for the management of neurological disorder.

<i>In Vivo</i>Sedative and Anxiolytic Activities of <i>Thunbergia erecta</i>(Acanthaceae) Leaves Activate Gamma-Aminobutyric Acid (GABA) Mediated Hyperpolarization in Swiss Albino Mice

Background: Thunbergia erecta (Acanthaceae) is the most abundant medicinal plant in different parts of Bangladesh where it is known as “nilghonta”. It has been used as traditional medicine for insomnia, depression and anxiety management. However, no scientific evidence of T. erecta belonging to neuropharmacological activity has been reported. The aim of present study was to investigate in vivo sedative and anxiolytic activities of methanol extract from the leaves of T. erecta in Swiss Albino mice. Methods: Sedative activity of METE was investigated using open field, hole cross and thiopental sodium-induced sleeping time test model whereas anxiolytic activity was screened by elevated-plus maze, light-dark box, hole-board and marble-burying test method in mice at 200 and 400 mg/kg doses. The acute toxicity study and phytochemical analysis of METE also carried out. Diazepam used as the positive control for the following behavioral pharmacology test. Results: METE exhibited significant (p Conclusion: The experimental result indicates T. erecta contains phytoconstituents that possess sedative and anxiolytic activity which traditionally used in insomnia, depression and anxiety management.

Propofol vs traditional sedatives for sedation in endoscopy:A systematic review and meta-analysis

BACKGROUND Propofol is commonly used for sedation during endoscopic procedures.Data suggests its superiority to traditional sedatives used in endoscopy including benzodiazepines and opioids with more rapid onset of action and improved postprocedure recovery times for patients.However,Propofol requires administration by trained healthcare providers,has a narrow therapeutic index,lacks an antidote and increases risks of cardio-pulmonary complications.AIM To compare,through a systematic review of the literature and meta-analysis,sedation with propofol to traditional sedatives with or without propofol during endoscopic procedures.METHODS A literature search was performed using MEDLINE,Scopus,EMBASE,the Cochrane Library,Scopus,LILACS,BVS,Cochrane Central Register of Controlled Trials,and The Cumulative Index to Nursing and Allied Health Literature databases.The last search in the literature was performed on March,2019 with no restriction regarding the idiom or the year of publication.Only randomized clinical trials with full texts published were included.We divided sedation therapies to the following groups:(1)Propofol versus benzodiazepines and/or opiate sedatives;(2)Propofol versus Propofol with benzodiazepine and/or opioids;and(3)Propofol with adjunctive benzodiazepine and opioid versus benzodiazepine and opioid.The following outcomes were addressed:Adverse events,patient satisfaction with type of sedation,endoscopists satisfaction with sedation administered,dose of propofol administered and time to recovery post procedure.Meta-analysis was performed using RevMan5 software version 5.39.RESULTS A total of 23 clinical trials were included(n=3854)from the initial search of 6410 articles.For Group I(Propofol vs benzodiazepine and/or opioids):The incidence of bradycardia was not statistically different between both sedation arms(RD:-0.01,95%CI:-0.03–+0.01,I2:22%).In 10 studies,the incidence of hypotension was not statistically difference between sedation arms(RD:0.01,95%CI:-0.02–+0.04,I2:0%).Oxygen desaturation was higher in the propofol group but not statistically different between groups(RD:-0.03,95%CI:-0.06–+0.00,I2:25%).Patients were more satisfied with their sedation in the benzodiazepine+opioid group compared to those with monotherapy propofol sedation(MD:+0.89,95%CI:+0.62–+1.17,I2:39%).The recovery time after the procedure showed high heterogeneity even after outlier withdrawal,there was no statistical difference between both arms(MD:-15.15,95%CI:-31.85–+1.56,I2:99%).For Group II(Propofol vs propofol with benzodiazepine and/or opioids):Bradycardia had a tendency to occur in the Propofol group with benzodiazepine and/or opioidassociated(RD:-0.08,95%CI:-0.13–-0.02,I2:59%).There was no statistical difference in the incidence of bradycardia(RD:-0.00,95%CI:-0.08–+0.08,I2:85%),desaturation(RD:-0.00,95%CI:-0.03–+0.02,I2:44%)or recovery time(MD:-2.04,95%CI:-6.96–+2.88,I2:97%)between sedation arms.The total dose of propofol was higher in the propofol group with benzodiazepine and/or opiates but with high heterogeneity.(MD:70.36,95%CI:+53.11–+87.60,I2:61%).For Group III(Propofol with benzodiazepine and opioid vs benzodiazepine and opioid):Bradycardia and hypotension was not statistically significant between groups(RD:-0.00,95%CI:-0.002–+0.02,I2:3%;RD:0.04,95%CI:-0.05–+0.13,I2:77%).Desaturation was evaluated in two articles and was higher in the propofol+benzodiazepine+opioid group,but with high heterogeneity(RD:0.15,95%CI:0.08–+0.22,I2:95%).CONCLUSION This meta-analysis suggests that the use of propofol alone or in combination with traditional adjunctive sedatives is safe and does not result in an increase in negative outcomes in patients undergoing endoscopic procedures.

Maintenance time of sedative effects after an intravenous infusion of diazepam: A guide for endoscopy using diazepam

AIM: To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP ) 2C19 genotypes after an infusion regimen of diazepam commonly used forgastrointestinal endoscopy in Japan. METHODS: Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical ? icker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg). RESULTS: The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P < 0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests. CONCLUSION: With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.

An Easy Way for Percutaneous Nephrolithotomy Using Mixed Sedative Agents

Objective: We recorded the data of patients performing Percutaneous Nephro-lithotomy (PCNL) under combined spinal anesthesia with sedative mixtures of Ketamine-Propofol (KP) or Fentanyl-Propofol (FP). Background: The PCNL is usually done under General anesthesia (GA);combining spinal anesthesia with a mixture of sedative drugs has shown to provide an optimum intra and post-operative analgesic and sedative response without side effects. Patients and Methods: 100 healthy patients were enrolled for PCNL, after stabilization of the sensory block of spinal anesthesia patients were randomized into two groups;Group KP received 1 mg/Kg Ketamine and 1 mg/Kg Propofol diluted in 20 ml syringe given over 30 seconds and Group FP received 1 mic/Kg Fentanyl and 1 mg/Kg Propofol diluted in 20 ml syringe over 30 seconds;both groups will receive increment doses if the patient suffers from anxiety, pain or discomfort. Perioperative Hemodynamic data (HR, SBP, DBP, RR, and SpO2) were recorded;PACU stay time and post operative analgesia time were analyzed. Results: Sedative mixtures of FP and KP provided remarkably deep sedation levels for PCNL procedures under spinal anesthesia. Respiratory depression, hypotension and bradycardia were the major side effects reported in FP group which had mean decrease in RR of 4.63 breath/min (27.49%) with mean 3.77% drop in SpO2 levels. KP group produced significant increase in HR about 7 beats/min without reported side effects. Conclusion: Various sedation techniques may be applicable for PCNL procedures with routine premedication, mixtures of fentanyl-Propofol or Ketamine-Propofol could be used, and KP has advantages of stable hemodynamics, prolonged analgesic response intra and post-operatively with no appreciable side effects and more effective method of sedative mixture.

Effect of Suan Zao Ren (Semen Ziziphi Spinosae) Extract on the TXNIP/NLRP3 Pathway in Insomniac Rats

Objectives This study aimed to investigate the therapeutic effects of Suan Zao Ren(Semen Ziziphi Spinosae,SZS)extract on insomnia induced by p-chlorophenylalanine(PCPA)in rats and its influence on the thioredoxin-interacting protein(TXNIP)/nucleotide-binding domain Leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammasome pathway,and to preliminarily explore themechanism by which SZS extract improves insomnia.Methods Fifty male Sprague–Dawley(SD)rats were used,with 8 rats in the blank group and 42 rats in the modeling group.The modeling group was induced by intraperitoneal injection of PCPA at a dose of 500mg·kg^(-1) for six consecutive days,with daily cage exchange.After 6 days,40 successfully modeled rats were randomly divided into five groups:themodel group(equal volume of distilled water),the positive group(0.75 mg·kg^(-1)),and low-,medium-,and high-dose SZS extract groups(1.5,3,and 6 g·kg^(-1),respectively),with 8 rats in each group.Treatments were administered for seven consecutive days.Enzyme-linked immunosorbent assay was used to measure levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA)in the rat cerebral cortex.The thiobarbituric acid(TBA)method was used to determine malondialdehyde(MDA)levels,and the hydroxylamine method was used to determine superoxide dismutase(SOD)levels.The 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)method was used to measure total antioxidant capacity(TAOC)in the cerebral cortex.Pathological changes in the cerebral cortex were observed,and Western blot was used to detect the protein expressions of TXNIP,NLRP3,apoptosis-associated speck-like protein containing a Caspase activation and recruitment domain(CARD),and cysteine–aspartate-specific protease 1(Caspase-1)in the cerebral cortex.Results Compared with the blank group,the model group showed a significantly prolonged sleep latency(p<0.001)and a significantly shortened sleep duration(p<0.001).There were no changes in serum MDA and SOD levels.MDA levels in the cerebral cortex were significantly increased(p<0.001),while SOD and TAOC levels were significantly decreased(p<0.001).The 5-HT level was increased(p<0.05),and the GABA level was significantly decreased(p<0.001).SZS extract improved these conditions to varying degrees.Light microscopy showed no significant changes in cortical neurons but transmission electron microscopy revealed intact mitochondrial structures in the blank group,while the model group showed swollen and unclear mitochondria with reduced organelles.After 7 days of treatment,these conditions improved in the SZS extract groups.Compared with the blank group,the expressions of the four proteins in the model group were increased,and the expressions of these proteins were decreased in the SZS extract groups compared with the model group.Conclusion SZS extract may exert an antioxidant effect to treat insomnia by downregulating the expression of TXNIP/NLRP3 proteins and regulating oxidative stress levels in the cerebral cortex.

Inhaled volatile anesthetics in the intensive care unit

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Sedative and Hypnotic Effects and Transcriptome Analysis of Polygala tenuifolia in Aged Insomnia Rats

Objective:To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia(PT)on treating aged insomnia rats.Methods:Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table,including control group,model group,diazepam group(0.92 mg/kg),as well as PT low-,medium-and high-dose groups(0.0875,0.175,0.35 g/kg,respectively),10 rats in each group.Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days.PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment.Then the rats were investigated by body weight,Morris water maze test,pentobarbital test,enzyme-linked immunosorbent assay,and transcriptome sequencing.Results:Compared with the model group,PT increased the body weight,improved memory ability,and prolonged pentobarbital-induced sleep time of aged insomnia rats(P<0.01 or P<0.05).The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine(5-HT)and gamma-aminobutyric acid(GABA),and decreased the level of Glu in the hippocampus of aged insomnia rats(P<0.05 or P<0.01).Twenty-four differentially expressed genes(DEGs)were overlapped among model group,medium-dose PT group,and diazepam group in transcriptome analysis.Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT(P<0.01 or P<0.05).The metabolic pathways of PT were relatively less than diazepam(91 vs.104).Conclusions:The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro,metabolism pathways,especially through GABAergic signaling pathway.It provided more effective herb choice for the treatment of senile insomnia.

Safety and efficacy comparison of remimazolam and propofol for intravenous anesthesia during gastroenteroscopic surgery of older patients:A meta-analysis

BACKGROUND Remimazolam is characterized by rapid action and inactive metabolites.It is used as the general anesthetic for many clinical surgeries.In this study,we performed a meta-analysis to evaluate whether remimazolam is superior to propofol for gastroenteroscopy in older patients.AIM To compare the adverse events and efficacy of remimazolam and propofol during gastroenteroscopy in older adults.METHODS The PubMed,Web of Science,the Cochrane Library databases were queried for the relevant key words"remimazolam,""and propofol,""and gastrointestinal endoscopy or gastroscopy."The search scope was"Title and Abstract,"and the search was limited to human studies and publications in English.Seven studies wherein remimazolam and propofol were compared were included for the metaanalysis.RESULTS We selected seven randomized controlled trials involving 1445 cases for the analysis.Remimazolam reduced the hypotension(relative risk,RR=0.44,95%CI:0.29-0.66,P=0.000),respiratory depression(RR=0.46,95%CI:0.30-0.70,P=0.000),injection pain(RR=0.12,95%CI:0.05-0.25,P=0.000),bradycardia(RR=0.37,95%CI:0.24-0.58,P=0.000),and time to discharge[weighted mean difference(WMD)=-0.58,95%CI:-0.97 to-0.18,P=0.005],compared to those after propofol administration.No obvious differences were observed for postoperative nausea and vomiting(RR=1.09,95%CI:0.97-1.24,P=0.151),dizziness(RR=0.77,95%CI:0.43-1.36,P=0.361),successful sedation rate(RR=0.96,95%CI:0.93-1.00,P=0.083),or the time to become fully alert(WMD=0.00,95%CI:-1.08-1.08,P=0.998).CONCLUSION Remimazolam appears to be safer than propofol for gastroenteroscopy in older adults.However,further studies are required to confirm these findings.

Sedative–hypnotic effect of YZG-330 and its effect on chloride influx in mouse brain cortical cells

This study was to examine the sedative–hypnotic effect of YZG-330 and its influence on Cl−influx in mouse cortical cells.In a sleep time-prolongation test in which mice were administered a threshold dosage of sodium pentobarbital(ip),YZG-330(0.125,0.5 and 2 mg/kg,po)prolonged the sleep time by 25%(P40.05),64%(Po0.01)and 506%(Po0.001),respectively.Thereafter,treatment with YZG-330 permitted mice that had woken up after the threshold dose of sodium pentobarbital(ip)to fall asleep again.A Cl−-sensitive fluorescent probe,N-(ethoxycarbonylmethyl)-methoxyquinolinium bromide(MQAE),was used to determine the effect of YZG-330 on Cl−influx.YZG-330(0.3,0.6 and 1.5 mM)increased Cl−influx in mouse cortical cells in a concentration-dependent manner.These data suggest that YZG-330 has a hypnotic effect in mice,and the effect may be related to an increase in Cl−influx in cortical cells.

Efficacy and safety of remimazolam in bronchoscopic sedation:A meta-analysis

BACKGROUND Remimazolam is a new benzodiazepine used for procedural sedation and general anesthesia.Several studies have used remimazolam for bendable bronchoscopy.AIM To assess the safety and efficacy of remimazolam for sedation in patients undergoing bendable bronchoscopy by performing a meta-analysis of randomized controlled trials(RCTs).METHODS We searched the EMBASE,PubMed,Cochrane Library,and Web of Science databases for RCTs on bendable bronchoscopic procedural sedation with remimazolam vs conventional sedatives(CS).RESULTS Five studies with 1080 cases were included.Remimazolam had the same sedation success rate compared with CS[relative risk(RR):1.35,95%CI:0.60-3.05,P=0.474,I2=99.6%].However,remimazolam was associated with a lower incidence of hypotension(RR:0.61;95%CI:0.40-0.95,P=0.027;I2=65.1%)and a lower incidence of respiratory depression(RR:0.50,95%CI:0.33-0.77,P=0.002,I2=42.3%).A subgroup analysis showed a higher success rate of sedation with remimazolam than midazolam(RR:2.45,95%CI:1.76-3.42,P<0.001).Compared with propofol,the incidence of hypotension(RR:0.45,95%CI:0.32-0.64,P<0.001,I2=0.0%),respiratory depression(RR:0.48,95%CI:0.30-0.76,P=0.002,I2=78.4%),hypoxemia(RR:0.36,95%CI:0.15-0.87,P=0.023),and injection pain(RR:0.04,95%CI:0.01-0.28,P=0.001)were lower.CONCLUSION Remimazolam is safe and effective during bronchoscopy.The sedation success rate was similar to that in the CS group.However,remimazolam has a higher safety profile,with fewer inhibitory effects on respiration and circulation.