The primary aim of this study was to evaluate the sedative effects of injectable acepromazine 2 mg/mL when administered to dogs via the oral transmucosal route. The secondary objective was to assess the cardiovascular and haemodynamic effects of oral transmucosal acepromazine. A single centre, prospective, randomised, blinded, controlled clinical trial, including a total of 28 client-owned adult healthy dogs (ASA I and II), undergoing elective surgical procedures. Patients were randomised into either a treatment group (A) receiving oral transmucosal acepromazine 0.05 mg/kg or a control group (C) receiving an equivalent oral transmucosal volume of water. Baseline values of sedation score, heart rate and non-invasive blood pressure were obtained prior to dose administration and repeated 1 hour later. Sedation scores in group A were significantly higher after treatment compared to baseline and were significantly higher than group C at the same time point. Heart rate and non-invasive blood pressure values significantly decreased following oral transmucosal acepromazine administration in group A and were significantly lower than group C at the same time point. Oral transmucosal acepromazine significantly increases sedation scores and decreases heart rate and non-invasive blood pressure 1 hour following administration. These findings support the administration of oral transmucosal acepromazine for pre-hospital sedation in healthy dogs.

ABSTRACTIntroductionInsomnia and other sleep disorders are becoming increasingly prevalent worldwide, while current sedative medications such as benzodiazepines, though effective, are often limited by side effects and dependency risks. Therefore, identifying safe natural compounds with sedative potential is of growing scientific and clinical interest. L‐quebrachitol (LQL), a naturally occurring cyclitol compound with antioxidant, antimicrobial, and antidiabetic properties, has not been previously evaluated for its sedative effects. The aim of this study is to evaluate the potential sedative effects of LQL through both in vivo and in silico methods.MethodsIn this experiment, 2‐day‐old broiler chicks (Gallus gallus domesticus) were given thiopental sodium (10 mg/kg, intraperitoneal [ip]) to induce sleep. LQL (1, 5, and 10 mg/kg, ip) and diazepam (2 mg/kg, ip) were administered alone or together to assess their synergistic or antagonistic effects on chicks. To assess its potential for interacting with the GABAA receptor (α1 and β2 subunits), a molecular docking study was carried out.ResultAccording to the in vivo investigation, the results indicate that LQL decreased the latency period while extending the animal's sleep duration time in a dose‐dependent manner. Moreover, the combination of LQL‐10 (10 mg/kg) and diazepam 2 (2 mg/kg) showed (p < 0.05) enhanced sedative effects significantly by decreasing latency time and prolonging sleeping duration. In addition, LQL has a moderate binding affinity of −5.3 kcal/mol against the GABAA receptor (α1 and β2 subunits), but forms strong hydrogen bond interactions and similar amino acid residues with standard drug diazepam, suggesting potential therapeutic effects. Further, LQL also demonstrated promising pharmacokinetic properties and low toxicity.ConclusionThese findings collectively enhance the potential of LQL as an effective sedative therapeutic agent. However, further research, including in vitro studies to confirm the molecular interactions and membrane permeability, followed by well‐designed clinical trials, is necessary to fully establish LQL as a safe and effective sedative agent.

A BSTRACT Background: Anxiety and insomnia are prevalent global health issues with limited effective treatments. Viola odorata L. (sweet violet) is traditionally known for its calming effects, although scientific validation remains sparse. Objective: This study investigated the sedative and anxiolytic potential of violet oil derived from V. odorata using phytochemical profiling, network pharmacology, and animal behavioral models. Materials and Methods: Bioactive constituents of violet oil were identified using gas chromatography-mass spectrometry (GC-MS). Network pharmacology analysis predicted molecular targets and pathways. Swiss albino mice were orally administered violet oil (2, 4, or 8 mg/kg), with diazepam (1 mg/kg, i.p.) and vehicle serving as controls. Behavioral assays – rota-rod, elevated plus maze, actophotometer, light-dark box, and hole board – evaluated sedative and anxiolytic effects. Results: GC-MS identified 36 compounds, notably humulene (45.3%), alpha-ionone (15.88%), caryophyllene (9.88%), and alpha-isomethyl ionone (9.71%). Network pharmacology revealed 23 potential targets and 17 pathways, including those related to circadian rhythm and thyroid hormone signaling. Violet oil at 8 mg/kg significantly increased falls in the rota-rod test ( P &lt; 0.05), indicating muscle relaxation. In the elevated plus maze, doses of 2 and 8 mg/kg increased time spent in open arms ( P &lt; 0.01 and P &lt; 0.05), suggesting anxiolytic activity. All doses reduced locomotor activity ( P &lt; 0.05 to P &lt; 0.001) and increased time in the illuminated area of the light-dark box ( P &lt; 0.05 to P &lt; 0.01), comparable to diazepam. Conclusion: Violet oil from V. odorata exhibits notable sedative and anxiolytic effects, likely mediated via multiple pathways involving terpenes and ionones. These results support its traditional use for anxiety and sleep disorders and suggest its potential as a natural therapeutic agent.

ABSTRACTBackgroundAlcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal‐related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol‐related behaviors. We investigated the effects of pitolisant, an FDA‐approved H3R antagonist, on ethanol (EtOH)‐related behaviors in mice.MethodAdult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted.ResultPitolisant administration reduced acute EtOH‐induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression‐like behavior during 24‐h withdrawal (Post‐EtOH). Mechanistically, the Post‐EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra‐LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol‐related behavior.ConclusionThese findings highlight the HAergic system as a critical regulator of alcohol‐related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD.

The research focused on Wedelia montana (Blume) Boerl because of its numerous medicinal applications. W. montana belongs to the Asteraceae family. This investigation is intended to analyze the phytochemical content of the methanol extract of W. montana (MEWM) and evaluate its biological features by utilizing in vitro and in vivo models. In vitro examinations determined antioxidant capability, cytotoxic, anthelmintic, and thrombolytic activity of the MEWM. Furthermore, in vivo research included testing for the effects of antidepressants (TST and FST), effects on anxiety (LDT, HBT, and EPM), activities of sedatives (HCT and OFT), and analgesic activities (formalin‐induced licking test and tail immersion test). Treatment with MEWM exhibited potent antioxidant properties, with a cytotoxicity test revealing an LC50 value of 256.2 μg/mL, in contrast to 142.28 μg/mL for the positive control. It also resulted in the shortest times for paralysis and mortality at the highest dosage in the anthelmintic assay and notable thrombolytic activity (p < 0.0001). Moreover, MEWM has shown considerable efficacy contingent upon the FST, TST, EPM, HBT, and LDT dose and sedative effects in the OFT and HCT. A 200 mg/mL dosage in the analgesic assessment had no significant impact on the tail immersion test. However, MEWM demonstrated substantial analgesic action in the formalin‐induced paw‐licking experiment (p < 0.0001). The data indicate that MEWM is a potential source of antioxidant, cytotoxic, anthelmintic, thrombolytic, antidepressant, anxiolytic, sedative, and antinociceptive compounds. Further research is necessary to comprehend its therapeutic benefits completely.

Severe brain injury patients often require effective analgesia and sedation to manage pain, agitation, and inflammatory responses, which can impact clinical outcomes. This study aimed to analyze the effects of ketamine combined with remifentanil on analgesic sedation and inflammatory factors in patients with severe brain injury. Sixty patients were randomly divided into a remifentanil-only control group and a ketamine combined with remifentanil group. VAS, SAS, BCS, Ramsay scores, inflammatory factors (TNF-α, IL-2), and adverse reactions were compared. Compared with pre-operative levels, both groups showed significant reductions in VAS, SAS scores, TNF-α, and IL-2 (P < 0.05). Compared with the control group, the combined group exhibited significantly lower VAS and SAS scores, higher Ramsay sedation and BCS scores, and lower TNF-α and IL-2 levels (P < 0.05). There was no statistically significant difference in adverse reactions between groups (P > 0.05). Ketamine combined with remifentanil provides better analgesic and sedative effects in severe brain injury patients, effectively reducing pain and agitation, improving comfort, and suppressing inflammatory responses, demonstrating good clinical application value.

Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.

Green aroma technology represents an eco-friendly and sustainable approach to indoor air freshening through the use of herbal ingredients and plant-derived aromatic compounds such as essential oils, herbal extracts, and volatile phytoconstituents, they are designed to improve indoor air quality by imparting a pleasant fragrance while minimizing the health and environmental risks associated with synthetic air fresheners. Conventional air fresheners often contain synthetic fragrances and volatile organic compounds that pose potential health and environmental risks. Increasing awareness of the adverse effects of chemical fragrances, including respiratory irritation, allergies, and environmental pollution, has led to growing interest in herbal and eco-friendly alternatives. Generally herbal room fresheners commonly incorporate essential oils from plants such as Cymbopogon citratus (lemongrass), Ocimum sanctum (tulsi), Eucalyptus globulus, Lavandula angustifolia (lavender), Mentha piperita (peppermint), and Citrus species. These plants not only provide fragrance but also possess antimicrobial, antifungal, insect-repellent, and mood-enhancing properties. The presence of bioactive compounds such as terpenoids, phenolics, and flavonoids contributes to their functional benefits. Origanum majorana, Cymbopogon citratus were used in the preparation of room fresheners contains various terpenoids, phenolic, tannins and volatile oils show antimicrobial, anti-oxidant, anti-inflammatory and antispasmodic, anxiolytic and sedative effect. Formulation was prepared in the form of spray evaluated and compared with marketed formulation shows satisfactory results.

BackgroundAlcohol mixed with energy drinks (AmED) has emerged as a public health concern, particularly among young adults. Evidence shows that combining energy drinks (EDs) with alcohol can mask ethanol’s sedative effects, promoting higher intake and risky behaviors.MethodsA cross-sectional online survey was conducted among university students in the Mazovia region of Poland (July 2025). An anonymous questionnaire assessed sociodemographic characteristics, EDs consumption, AmED use, co-use of psychoactive substances, consumption contexts, and adverse effects. Associations were analyzed using chi-square tests and logistic regression.ResultsA total of 871 students (mean age = 22.1 ± 3.05 years; 73.2% women) participated. One in four (25.5%) reported at least occasional AmED use. Logistic regression showed that a later age of first energy drink consumption was associated with a higher likelihood of AmED (OR = 1.34; 95% CI: 1.14–1.56; p<0.001). Gender was the only significant sociodemographic predictor. Men were more likely to report co-consumption (OR = 1.37; 95% CI: 1.00–1.86; p < 0.05). Over half did not mix energy drinks with other substances; when they did, nicotine (e-cigarettes) and caffeine (coffee) were the most common. The main AmED social contexts were parties and studying, differing by gender. About one-third (36.7%) of AmED users experienced reported unspecified self-reported adverse effects.ConclusionsAmED consumption is common among university students from the Mazovia region of Poland and appears to be associated with contextual factors, while age of ED initiation showed an ordinal association with the likelihood of AmED use. These findings may inform prevention strategies addressing social drinking contexts and promoting responsible attitudes toward stimulant–alcohol co-use among young adults.

Aromatherapy, the use of essential oils for therapeutic purposes, has been a staple of traditional medicine for centuries, offering a range of health benefits, particularly for improving sleep quality. This review explores the role of aromatherapy in enhancing sleep, focusing on both traditional practices and the growing body of scientific evidence supporting its efficacy. Aromatherapy is commonly employed to address sleep disorders such as insomnia, anxiety-induced sleep disturbances, and circadian rhythm imbalances. The use of essential oils such as lavender, chamomile, and valerian has been particularly highlighted for their calming and sedative effects, which contribute to better sleep quality. Traditional practices, rooted in various cultures, have long utilized these oils in conjunction with other modalities, such as massage and inhalation, to promote relaxation and sleep. Recent scientific studies have validated many of these traditional claims, indicating that aromatherapy can indeed improve sleep quality by reducing sleep latency, enhancing deep sleep stages, and mitigating stress and anxiety. Additionally, the physiological mechanisms underlying these effects, including the modulation of neurotransmitter activity and the impact on autonomic nervous system regulation, are discussed. This review examines both historical applications of aromatherapy and contemporary clinical research, providing a comprehensive understanding of its role in sleep management. Given the global rise in sleep disorders and the increasing interest in non-pharmacological treatments, aromatherapy emerges as a promising and accessible approach for improving sleep quality. This paper aims to synthesize the available evidence, offering insights into the therapeutic potential of aromatherapy and proposing directions for future research.

Allergic rhinitis (AR) and chronic urticaria (CU) are prevalent conditions in children worldwide, including in the Asia-Pacific (APAC) region. These conditions are associated with a substantial impact on health-related quality of life (HRQoL), affecting many aspects of children’s daily functioning. Bilastine 10 mg orodispersible tablet (ODT) is a non-sedating second-generation H1-antihistamine indicated in Asia for the symptomatic treatment of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria in children aged 6–11 years with a body weight of ≥20 kg. Real-world evidence on the use of second-generation H1-antihistamines, particularly bilastine 10 mg ODT, in paediatric populations in APAC remains limited. We present thirteen clinical-practice cases from experienced allergologists, dermatologists, ENT specialists, and paediatricians from APAC, discussed at the STAR NETWORK Expert Panel meeting. The cases illustrate the clinical use, efficacy, and safety of bilastine 10 mg ODT once daily in children aged 6–11 years with AR or CU, across a diverse range of clinical aetiologies and symptoms. Once-daily bilastine 10 mg ODT was found to be effective and well-tolerated in managing AR and CU in school-going children, improving symptom control compared with other antihistamines, without any sedative effects or other adverse events.

To evaluate the efficacy and safety of combinations of oral midazolam and esketamine for pediatric preoperative sedation. Children aged 1‒6-years undergoing elective surgery were assigned to Group A (0.62 mg/kg midazolam and 2.05 mg/kg esketamine), Group B (0.41 mg/kg midazolam and 4.1 mg/kg esketamine), and Group C (0.21 mg/kg midazolam and 6.16 mg/kg esketamine). The combination was administered orally before anesthesia induction. Primary outcome was sedation success, defined as a modified Ramsay sedation score ≥3a, low parent-child separation anxiety, and acceptance of the face mask for inhalation induction. Secondary outcomes included parental satisfaction, occurrence of Adverse Events (AE), and recovery times. The sedation success rate in Group B was 71.8%, which was significantly higher than Group A (53.5%, p < 0.05) but not Group C (68.2%, p > 0.05). There was no difference in the sedation success rate between Group A and Group C (p > 0.05). The overall incidence rate of AE in Group C was 25.90%, which was significantly higher than that in Group A (2.30%) and Group B (4.70%) (p < 0.05). No significant differences in sedation success rates were observed between genders within each group (p > 0.05). The combination of 0.41 mg/kg midazolam and 4.1 mg/kg esketamine provided the most effective sedation with the fewest adverse events in pediatric patients. This regimen may reduce rescue sedation needs and improve perioperative flow. http://www.chictr.org.cn (ChiCTR2400080633; date of first registration: February 4th, 2024).

Introduction: The Laryngeal Mask Airway (LMA) is a supraglottic device designed to secure the airway during minor to moderate surgical procedures. Second-generation LMAs, such as the ProSeal LMA (PLMA), offer enhanced safety features, including a gastric drain to reduce the risk of aspiration. Optimal insertion conditions depend on effective sedation with agents like propofol and adjuvants such as dexmedetomidine, which provide stable haemodynamics and suppress airway reflexes. Aim: To compare dexmedetomidine and midazolam as coinduction agents with propofol for ProSeal laryngeal mask airway (PLMA) insertion, assessed using the Muzi scoring system. Materials and Methods: This prospective, randomised controlled trial was conducted at the Department of Anaesthesiology, ACS Medical College, Chennai, India, over a period of 16 months and included 60 patients scheduled for elective surgeries under general anaesthesia. Patients were randomly assigned to Group I (n=30) - dexmedetomidine (0.5 mcg/kg) with propofol (2.5 mg/ kg), or Group II (n=30) - midazolam (0.04 mg/kg) with propofol (2.5 mg/kg). PLMA insertion conditions, insertion time, first-attempt success rate, and haemodynamic stability were compared between the two groups using the t-test and Chi-square test. Results: There were no significant differences in age, gender, height, or weight between the groups. Group I demonstrated significantly better PLMA insertion conditions, including a higher first-attempt success rate (93.3% vs. 70%, p=0.019) and shorter insertion time (18.30±4.39 seconds vs. 21.27±6.21 seconds, p=0.04). Haemodynamic stability was superior in Group I, with lower heart rates (75.07±10.40 vs. 81.13±11.98 bpm, p=0.04) and lower systolic mean arterial pressures (115.67±5.70 vs. 119.93±5.69 mmHg, p=0.005 at 5 min; 117.20±4.69 vs. 121.07±4.83 mmHg, p=0.003 at 10 min). The requirement for additional propofol doses was lower in Group I (3.3% vs. 20%). The incidence of complications, such as sore throat (3.3% in Group I vs. 10% in Group II) and patient movement, was minimal in both groups, with no significant differences. Conclusion: Dexmedetomidine, as a co-induction agent with propofol, significantly improves PLMA insertion conditions, reduces the need for additional propofol, and provides superior haemodynamic stability, suggesting it is a more effective adjunct for PLMA insertion than midazolam.

Association of medication-induced deep sedation and emotional distress during mechanical ventilation with loss of independent living: an observational cohort study.

Background:Tourniquet-related responses are a frequent clinical challenge during foot and ankle surgery under peripheral nerve block. Pharmacologic sedation and analgesia represent a common approach. Ciprofol, a novel intravenous sedative, remains underexplored in this surgical context.Objective:This study aimed to evaluate the impact of ciprofol-assisted sedation on tourniquet-related responses in patients undergoing foot and ankle surgery.Design:In total, 240 patients scheduled for foot and ankle procedures under peripheral nerve block with the use of a high thigh tourniquet were enrolled and randomized to undergo ciprofol (Group C) or propofol (Group P) sedation.Methods:In Group C, ciprofol was administered at an initial rate of 0.5 mg/(kg·h), with maintenance doses ranging from 0.5 to 2 mg/(kg·h) to maintain a BIS (bispectral index) between 65 and 80. Group P received an initial infusion of propofol at 2 mg/(kg·h), with maintenance between 2 and 8 mg/(kg·h). Primary outcomes included the incidence of intraoperative rescue analgesia and body movement. Secondary outcomes encompassed hemodynamic fluctuations, anesthesia success rate, injection-related discomfort, respiratory depression, blood pressure abnormalities, postoperative complications, and long-term complications.Results:There were no significant differences between groups in terms of the need for rescue analgesia or body movement during surgery. However, patients in the ciprofol group experienced significantly lower rates of injection pain and intraoperative hypotension relative to the propofol group (p < 0.05). No significant differences were found in postoperative adverse effects or long-term complications. In addition, both anesthesia completion rates and physician/patient satisfaction scores were similar between the two groups.Conclusion:BIS-guided sedation with ciprofol during foot and ankle surgery provides equivalent control of tourniquet-related responses compared to propofol. However, ciprofol demonstrates superior intraoperative hemodynamic stability and a more favorable safety profile, including reduced adverse event rates.Trial Registration:http://www.chictr.org.cn; ChiCTR2400083924; May 7, 2024.

There is growing concern regarding potential neurotoxicity and long-term neuro-cognitive outcomes in young children receiving general anesthetics (GAs) and sedatives. Most currently used anesthetics and sedatives have shown to be potentially neurotoxic in animal studies. However, three landmark human studies have provided compelling evidence that a single brief exposure to GAs at an early age does not affect neurocognitive or behavioral outcomes. It is unclear if multiple exposures to GAs and sedatives in early childhood lead to worse neurocognitive or behavioral outcomes. This review article will summarize the evidence in both animal and human studies and discuss the limitations in both. Furthermore, we will suggest strategies to limit GA and sedative exposure in young children, as well as propose future directions of study.

PurposeDexmedetomidine is commonly used for its sedative and neuroprotective effects, but its impact on brain activity and sleep architecture is not fully understood. Emerging evidence suggests it may improve postoperative outcomes, particularly in older adults, by promoting sleep-like states with stable hemodynamics, reducing posttraumatic stress, and decreasing delirium. This study aims to better characterize the neurophysiological profile of dexmedetomidine-induced sedation by comparing it to natural sleep in both young and aged mice.MethodsTwelve 4–5 month old and six 10–18-month-old C57BL/6 J male mice were used. Animals were implanted with electroencephalography/electromyography electrodes. After at least 7 days of recovery, animals received intraperitoneal injections of saline or dexmedetomidine (50–400 µg/kg) and sleep–wake states were recorded for 5–12 h.ResultsDexmedetomidine significantly increased delta (0.5–4 Hz) power beyond levels observed during natural non-rapid eye movement (NREM) sleep, followed by suppression of both high frequency (> 10 Hz) electroencephalography activity and REM sleep in a dose dependent manner. Body posture was sprawled during dexmedetomidine versus curled as during natural sleep. Notably, at the transition into sedation, dexmedetomidine induced high-voltage spikes resembling high-voltage spindles and spike wave discharges. These spikes were more prominent in the prefrontal cortex compared to the parietal cortex and aged animals exhibited more high voltage spikes than young adult animals.ConclusionThe combination of elevated delta power, high-voltage spikes, suppression of high-frequency activity, and sprawled body posture during dexmedetomidine-induced sedation indicates a state of unconsciousness that is neurophysiologically distinct from natural NREM sleep in mice. These findings highlight important age-related differential responses to dexmedetomidine and help inform its safe and effective use in vulnerable patient populations.

From over-the-counter to criminal evidence: Pharmacological profiles, analytical methods, and forensic insights into diphenhydramine's role in drug-facilitated crime.

Insomnia, a widespread neurological condition, is often managed with diazepam (DZP), a gamma-aminobutyric acid A (GABAA) receptor agonist, though prolonged use raises concerns about dependence and cognitive impairment. This study investigated the sedative and locomotor-suppressive effects of succinic acid (SUC), alone and in combination with DZP, supported by behavioral and computational analyses. Swiss albino mice were treated intraperitoneally (i.p.) with SUC (5, 10, 15mg/kg), DZP (2mg/kg), and their combination (SUC 10 + DZP 2mg/kg), followed by thiopental sodium (TS)-induced sleep and locomotor activity tests. SUC significantly reduced sleep latency and extended sleep duration in a dose-dependent manner, with the combination group showing the most potent synergistic effect (sleep duration: 185.14 ± 2.73min). In the open-field and light-dark tests, SUC suppressed locomotor activity and enhanced dark residence time (DRT), further confirming central nervous system (CNS) depressant effects. In silico docking to the GABAA receptor (PDB: 6X3X) revealed that SUC, despite having lower binding affinity (-4.1kcal/mol) than DZP (-8.4kcal/mol), formed more hydrogen bonds with key residues, suggesting stable and supportive receptor engagement. Pharmacokinetic (PK) profiling showed SUC is highly water-soluble, moderately absorbed (71.75%), poorly blood-brain barrier (BBB)-penetrant, and exhibits low toxicity (lethal dose 50 (LD50) = 2260mg/kg). These findings support SUC's potential as a safe, effective sedative agent, capable of enhancing DZP efficacy while possibly reducing its side effects. Future directions include exploring SUC derivatives with better brain penetration and validating these effects in clinical models.

Non-tracheal intubation anaesthesia for thoracoscopic surgery is associated with intraoperative hypoxaemia. Esketamine has both sedative and analgesic effects, which can increase lung compliance, reduce airway resistance and relax the respiratory smooth muscles. This study will investigate the effectiveness of low-dose esketamine in reducing the incidence of intraoperative hypoxaemia and other adverse events in patients undergoing thoracoscopic surgery without intubation anaesthesia. This randomised controlled trial will enrol patients scheduled for non-intubation video-assisted thoracoscopic surgery at Shandong Provincial Hospital Affiliated to Shandong First Medical University. Eligible participants will be randomly allocated in a 1:1 ratio to receive either the esketamine group or the normal saline (placebo) group. The primary outcomes are the incidence of hypoxaemia and the time to its onset, with hypoxaemia defined as an intraoperative pulse oximetry ≤90% lasting for at least 10 s. Secondary outcomes include the incidence of intraoperative hypercapnia (Partial pressure of carbon dioxide (PCO2) ≥60 mm Hg); concentrations of interleukin (IL)-6 and IL-8 at the end of surgery; postoperative Visual Analogue Scale scores; time to recovery of spontaneous respiration after laryngeal mask placement; time to laryngeal mask removal (measured from the end of surgery); awakening time; incidence of bradycardia (heart rate <60 beats per minute) and hypotension (a >20% reduction in blood pressure from the baseline value); incidence of ≤24-hour postoperative nausea and vomiting and hoarseness; time to ambulation, drinking and eating postoperatively; incidence of pulmonary complications within 2 weeks postoperatively; and length of hospital stay. All analyses will be performed based on using a modified intention-to-treat population principle. The study protocol has been reviewed and approved by the Ethics Committee of Shandong First Medical University Affiliated Provincial Hospital, with approval number SWYX 2025-714. The trial is also registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2400094821. On completion, the study findings will be prepared for publication and submitted to a relevant peer-reviewed journal. ChiCTR2400094821.