Significant Sedative Effects Research Articles

Efficacy and Safety of Combination of Noscapine and Chlorpheniramine in Management of Cold and Cough

Cough is one of the most common symptoms for which patients visit the doctor. Because of its broad differential diagnosis,cough is a challenging condition to manage. Antitussives or cough suppressants are indicated if cough interferes with dailyactivities. Cough suppressants not only provide symptomatic relief by decreasing cough, they also prevent the spread ofinfection. Noscapine is a non-narcotic cough suppressant, which relieves cough by acting at the level of the cough centerin the brain. It does not cause significant sedative, euphoric, or hypnotic effects, and other side effects such as respiratorysuppression and constipation that are typically associated with opioids. Hence, unlike other opioid antitussives such ascodeine, noscapine is nonaddictive.

Efficacy of Intravenous Low-Dose Ketamine for Prevention of Post-Spinal Anesthesia Shivering in Cesarean Section: A Double-Blind, Randomized Controlled Study

Background: Post-spinal anesthesia shivering in cesarean section is a common complication owing to sympatholysis, resulting in vasodilation and heat redistribution from the core to peripheral parts of the body. The physiological consequences of shivering include an increase in cardiac and systemic energy expenditure, oxygen consumption, and carbon dioxide production. Ketamine, a N-methyl D-aspartate (NMDA) receptor antagonist, has been reported to have anti-shivering effects. The aim of this study is to determine the effectiveness of prophylactic low-dose intravenous (IV) ketamine (0.25 mg/kg) in preventing shivering after spinal anesthesia as compared to placebo in elective cesarean sections. Methods: A randomized, double-blind study was conducted on 80 patients aged 18 to 40 years and American Society of Anesthesiologists grade II undergoing elective cesarean section under spinal anesthesia. Groups K and group S received IV ketamine 0.25 mg/kg diluted to 5 ml in normal saline and 5 ml normal saline IV, respectively, 10 minutes after spinal anesthesia. The incidence and duration of shivering, tympanic membrane temperature, sedation score, hemodynamic parameters, and side effects were recorded. Results: The incidence of shivering in group K was 12.5% compared to 32.5% in group S (P = 0.030). The mean duration of shivering was only 0.75 ± 2.02 min in group K as compared to 2.38 ± 3.57 min in group S (P = 0.014). Mean arterial pressure and heart rate were stable in group K without any significant sedative effect. Conclusion: The use of prophylactic low-dose ketamine (0.25 mg/kg) significantly reduces the incidence and duration of spinal anesthesia-induced shivering compared to placebo.

Application of superior iliac fascia block of inguinal ligament combined with patient controlled intravenous analgesia in elderly patients after hip arthroplasty

To compare the effect of patient-controlled intravenous analgesia(PCIA) and superior inguinal ligament iliac fascia block combined with PCIA after hip replacement in the elderly. Total of 82 elderly patients were treated with hip arthroplasty from June 2019 to June 2021 and randomly divided into observation group and control group. There were 42 patients in control group, including 18 males and 24 females, aged from 60 to 78 years old with an average of (70.43±3.67) years old, 28 femoral neck fractures and 14 femoral head necrosis, who received PCIA. The study group consisted of 42 cases, including 20 males and 22 females, aged from 61 to 76 years old with an average of (69.68±3.74) years old, 25 femoral neck fractures and 17 femoral head necrosis, who received superior inguinal ligament iliac fascia block combined with PCIA. Pain visual analogue scale (VAS) and Ramesay sedation scores at 2 h, 6 h, 12 h, 24 h and 48 h after operation were evaluated. In addition, the follow-up results of the total consumption of sufentanil and the total number of PCIA compressions at 48 hours after operation, the first time of landing after surgery, the time of hospital stay, the incidence of adverse reactions, the satisfaction with analgesia of two groups were observed. All patients were followed up for 9 to 24 months with an average of(13.85±2.67) months. There was no significant difference in operation time and intraoperative bleeding between two groups (P>0.05). There was no difference in VAS between two groups at 2 hours after operation (P>0.05), and the VAS of the study group at 6 h, 12 h, 24 h and 48 h after operation were lower than those of the control group(P<0.05). The Ramesay sedation scores of the study group at 2 h, 6 h and 12 h after operation were higher than those of the control group(P<0.05), and there were no differences in Ramesay score between two groups at 24 h and 48 h after operation (P>0.05). The consumption of sufentanil in the study group within 48 hours after operation was lower than that in the control group (P<0.05), and PCIA compression times were lower than those in the control group(P<0.05), and the time of first landing was earlier than that in the control group(P<0.05). There was no significant difference in hospital stay, adverse reaction rate, complications between two groups (P>0.05). The satisfaction of analgesia in the study group was higher than that in the control group (P<0.05). Superior iliac fascia block of inguinal ligament combined with PCIA has significant analgesic and sedative effects after hip arthroplasty in the elderly. It can reduce the amount of sufentanil used and the total number of PCIA compressions, which is conducive to the early activity of patients out of bed, improve the satisfaction of analgesia.

Evaluation of the Neurobehavioural Toxicity Potential of Aqueous Ethanol Extracts of Leaf/Seed of Datura metel, Mucuna pruriens, and Tapinanthus globiferus Growing on Azadirachta indica Host Tree in Mice

Aqueous ethanol extracts of Mucuna pruriens seed (AEMPS), Datura metel leaf (AEDML) and seed (AEDMS), and Tapinanthus globiferus (AETGL) Growing on Azadirachta indica host tree are being evaluated for their anxiolytic, antidepressant, anti-parkinsonian, and addictive activities in other studies. The aim of this study was to investigate the liability or otherwise of extracts of the selected medicinal plants for some benzodiazepines-related neurobehavioural toxicities in mice. Actophotometry was used for the evaluation of the locomotory activity related to central nervous system depressant (cns) effect, diazepam-induced sleep potentiation for hypnotic liability, rodent beam (rod)-walking assay for balance and motor co-ordination, and novel object recognition test (NORT) for cognitive deficit evaluation. The results indicate, compared to negative control (distilled water) treatment mean values of 4.69±0.95 % locomotory activity reduction, 430.71±16.80 sec. sleep onset and 168.43±10.56 min. duration, 5.00±0.00 balance/motor co-ordination performance, and 54.41±1.99 novel object recognition, treatments with high oral doses of AETGL and AEMPS (1500 mg/kg each) did not significantly negatively impact these behavioural indices but even enhanced novel object recognition. High oral doses of AEDML and AEDMS (750 mg/kg each), and tramadol (133 mg/kg) caused significant (p&lt;0.05) 42.24±2.64, 27.73±2.17, and 36.74±4.44, mean % locomotory activity reductions, 196.86±10.12, 193.88±15.39, and 189.14±18.31 second mean sleep onsets and 319.71±18.85, 309.57±20.27, and 356.00±26.01 minute mean sleep durations, 1.67±0.42, 1.30±0.40, 1.833±0.48 mean balance/motor co-ordination performances, and 40.49±5.45, 31.33±5.23, 19.37±3.96 mean novel object recognitions, respectively. Diazepam (2 mg/kg) treatment caused 33.71±2.19 mean % locomotory activity reduction, 1.33±0.49 mean balance/motor co-ordination performance, and 29.91±2.81 mean novel object recognitions. Additionally, most mouse groups exposed to tramadol, AEDML, and AEDMS extracts displayed unusual (hallucination-like, predator-like) fearful trepidations when in proximity with the novel objects. These findings indicate AETGL and AEMPS extracts may be devoid of neurobehavioural toxicities but tramadol, diazepam, AEDML and AEDMS extracts may be liable to significant sedative, hypnotic, myo-relaxant, and anti-cognitive effects. These findings justify the traditional uses of Tapinanthus species and Mucuna pruriens extracts for the treatment of memory deficits and related neurological disorders. They also justify the morbid and fatal toxicity risks associated with the use of Datura metel extracts, tramadol, and the benzodiazepines.

Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain.

Premenstrual dysphoric disorder is a female affective disorder that is defined by mood symptoms. The condition is linked to unstable progesterone concentrations. Progestin supplementation is given in cases of threatened or recurrent miscarriage and for luteal phase support. Progesterone is essential for implantation, immune tolerance, and modulation of uterine contractility. For a long time, the administration of progestins was associated with an unfavorable impact on mood, leading to negative affect, and, therefore, was contraindicated in existing mood disorders. Establishing the role of the natural progesterone derivative allopregnanolone in advances in the treatment of postpartum depression has shed new light on the general pathophysiology of mood disorders. Allopregnanolone directly interacts with gamma-aminobutyric acid type A (GABA-A) receptors even at nanomolar concentrations and induces significant anti-depressant, anti-stress, sedative, and anxiolytic effects. Postpartum depression is caused by a rapid drop in hormones and can be instantly reversed by the administration of allopregnanolone. Premenstrual dysphoric disorder can also be considered to result from insufficient neuroactive steroid action due to low progesterone derivative concentration, unstable hormone levels, or decreased receptor sensitivity. The decrease in progesterone levels in perimenopause is also associated with affective symptoms and an exacerbation of some psychosomatic syndromes. Bioidentical progesterone supplementation encounters several obstacles, including limited absorption, first-pass effect, and rapid metabolism. Hence, non-bioidentical progestins with better bioavailability were widely applied. The paradoxical, unfavorable effect of progestins on mood can be explained by the fact that progestins suppress ovulation and disturb the endocrine function of the ovary in the luteal phase. Moreover, their distinct chemical structure prevents their metabolism to neuroactive, mood-improving derivatives. A new understanding of progesterone-related mood disorders can translate the study results from case series and observational studies to cohort studies, clinical trials, and novel, effective treatment protocols being developed.

Comparative Assessment of Anxiety during Inferior Alveolar Nerve Block under Nitrous Oxide + Oxygen and Oxygen Inhalation Sedation in Children Aged 3-12 Years: A Randomized Clinical Trial.

A comparative evaluation of children's anxiety with the use of nitrous oxide-oxygen (N2O-O2) inhalation sedation during the administration of inferior alveolar nerve block (IANB). A total of 60 children between 3 and 12 years of age, with Frankl's behavior rating of 2-3 requiring IANB for any dental procedure were enrolled in this randomized clinical study. Group I (n = 30) received N2O and oxygen inhalation sedation at a concentration in the range of 25-50%, whereas group II (n = 30) received 100% O2 as a placebo. The physiological parameters like pulse rate, respiration, blood pressure, and O2 saturation were measured at the baseline, intraoperatively [during and after administration of local anesthesia (LA)] and postoperatively after the termination of the gases in both groups. The sedation level was measured intraoperatively (before administration of LA) using the Ramsay Sedation Score (RSS). The discomfort and anxiety were measured at the baseline, intraoperatively, and postoperatively using the Face, Legs, Activity, Cry, Consolability (FLACC) behavior scale. The data were evaluated using the statistical software International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) statistics 20.0. There was a significant difference in the FLACC scores between the two groups, intraoperatively (p-value-0.002), and postoperatively (p-value-0.049). The mean of the RSS for group I was 2.80 + 1.03, and for group II was 1.80 + 0.81. All the physiological parameters recorded were within the normal range. The use of N2O-O2 inhalation improved the anxiety levels in children while receiving the IANB and showed significant anxiolytic and sedative effects as compared to O2 inhalation. Nitrous oxide-oxygen (N2O-O2) inhalation can be used as a nonpharmacological behavior management adjunct for invasive treatments for children with utmost comfort for the child. Thomas PS, Dave BH, Shah DJ, et al. Comparative Assessment of Anxiety during Inferior Alveolar Nerve Block under Nitrous Oxide + Oxygen and Oxygen Inhalation Sedation in Children Aged 3-12 Years: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2023;16(1):30-36.

Efficacy and safety of dexmedetomidine to prevent shivering in cesarean delivery under spinal anesthesia: a double-blind, randomized controlled trial

Background &amp; objective: Postoperative shivering is a source of much discomfort to the patients following spinal anesthesia (SA), especially in patients undergoing cesarean delivery. The anesthetists have employed various medications and a variety of measures to prevent shivering in their patients. The objective of this study was to investigate the efficacy and safety of intravenous (IV) dexmedetomidine in preventing shivering in patients undergoing cesarean delivery under SA.&#x0D; Methodology: This prospective, double-blind, randomized trial involved 62 parturients undergoing cesarean delivery under SA. They were randomly divided into two groups; patients in dexmedetomidine group (Group D, n = 31) received dexmedetomidine 0.5 µg/kg IV over 10 min followed by infusion of 0.4 µg/kg/h until the end of surgery; whilst patients in the control group (Group C, n = 31) received equivalent loading and infusion volume of 0.9% saline. Both groups were operated upon by a standardized spinal anesthesia technique. The occurrence of shivering, sedation score and hemodynamic parameters were recorded intraoperatively. The recording anesthetist was blinded regarding the study or the control groups.&#x0D; Results: The occurrence of shivering was significantly reduced in Group D as compared to Group C (3.2% vs 64.5%, P &lt; 0.001). Patients in Group D were more sedated as compared to Group C (51.6% vs 0%, P &lt; 0.001). There was no statistically significant difference in systolic and diastolic blood pressure readings between both of the groups. Heart rates in Group D were significantly lower than the Group C but still were within normal physiological range.&#x0D; Conclusion: IV dexmedetomidine was effective in reducing the occurrence of shivering but with significant sedative effect and lowering of heart rate than the placebo. Although the heart rates remained within normal range in both groups.&#x0D; Key words: Anesthesia, Spinal; Cesarean; Dexmedetomidine; Shivering&#x0D; Citation: Wan Md Adnan WAA, Wan Hassan WMN, Seevaunnamtum P, Omar SC, Nik Mohamad NA. Efficacy and safety of dexmedetomidine to prevent shivering in cesarean delivery under spinal anesthesia: a double-blind, randomized controlled trial. Anaesth. pain intensive care 2023;27(6):632−638; DOI: 10.35975/apic.v27i6.2346&#x0D; Received: January 09, 2023; Reviewed: January 29, 2023; Accepted: February 08, 2023

Comparative Study of the Effect of Oral Chloral Hydrate and Intranasal Fentanyl on Sedation in Children for Electroencephalography.

Sedation and stability during electroencephalography (EEG) in pediatrics have high clinical importance. This study compares the sedative properties of oral chloral hydrate (OCH) and intranasal fentanyl (INF). This study was a randomized clinical trial conducted in 2020 in Isfahan City on sixty-two pediatric candidates for EEG. Patients were randomized into two groups receiving 50 mg/kg OCH and 2 μg/kg INF thirty minutes before the process. The heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and oxygen saturation (O2 sat) of patients, sedation, and physician's satisfaction were measured and compared between groups. The HR of patients decreased significantly in both groups (P< 0.001), and the patients that received INF had significantly lower HR 15, 30, 45, and 60 minutes after drug administrations (P< 0.05). RR evaluation indicated significantly decreased RR in both groups (P< 0.001), and patients receiving INF had lower RR 30, 45, and 60 per minutes after drug administrations (P< 0.001). Both groups showed significantly increased sedation levels during the study (P< 0.001), and patients treated with INF had higher sedation levels 15, 30, and 45 minutes after drug administration. Satisfaction rates were higher among the group that received INF (P= 0.020). The use of INF had significant analgesic and sedative effects on pediatrics undergoing EEG.

Sedative-hypnotic effects of Boropinol-B on mice via activation of GABAA receptors.

Boropinol-B is a phenylpropanoid compound originally isolated from Boronia pinnata Sm. (Rutaceae). This study aimed to evaluate the sedative-hypnotic effects of Boropinol-B and explore the underlying mechanisms. Pentobarbital sodium-induced sleep mouse model and caffeine-induced insomnia mouse model were used to investigate the sedative effects of Boropinol-B. Pharmacokinetics profiles of Boropinol-B in rats were evaluated by high-performance liquid chromatography. The effects of Boropinol-B on the γ-aminobutyric acid (GABA)ergic system were investigated using ELISA assay and patch-clamp technique. Immunohistochemistry and immunofluorescence were carried out to assess the effects of Boropinol-B on sleep-related brain nucleus. Boropinol-B showed significant sedative effects, including reduced sleep latency, increased sleep duration in pentobarbital sodium-treated mice and decreased locomotor activity in insomnia mice. Pharmacokinetics studies demonstrated that Boropinol-B had a rapid onset of action, a short half-life and no accumulation. It increased the GABA level in mice's brain, and promoted chloride ions influx mediated by the γ-aminobutyric acid type A (GABAA) receptors in neurons. Also, it increased the c-Fos positive ratio of GABAergic neurons in ventrolateral preoptic nucleus and decreased c-Fos expression in tuberomammillary nucleus. Boropinol-B showed significant sedative-hypnotic effects in mice by activating the GABAA receptors and stimulating the sleep-related brain nucleus.

Zerumbone, a major sesquiterpene from Syringa pinnatifolia Hemsl., exerts the sedative effect by regulating GABAergic nervous system

Ethnopharmacological relevanceZerumbone (ZER) is a humulane sesquiterpenoid isolated from Syringa pinnatifolia Hemsl. (SP), its content accounts for 64.7% of volatile oil and 0.86% of total ethanol extract (TEE), representing one of characteristic ingredient of SP. As a representative Mongolian medicine with anti-“Khii”, anti-asthma, and clearing-heat effects, SP has been used for the treatment of cardiovascular diseases, upset, insomnia, and other symptoms. Aim of studyPrevious results showed that TEE has sedative effect, but the pharmacological substances and its sedative mechanism remains unclear. This study aims to determine whether ZER, as one of major and characteristic sesquiterpenoids of SP, contributes to the sedative effect of SP and its underlying mechanism. Materials and methodsLocomotor activity and threshold dose of pentobarbital sodium sleep experiments were used to evaluate the sedative effects in mice. ELISA assay was used to examine the level of GABA/Glu ratio in rats hippocampus, cortex and hypothalamus tissue. The binding ability of ZER with glutamic acid decarboxylase 67 (GAD67) and Gephyrin protein were predicted by molecular docking. Western blot and Immunohistochemistry assay were used to determine the expression of GABAergic nerve system related proteins (GAD67, Gephyrin) in rat’s hypothalamus. ZER was co-administrated with flumazenil and bicuculline (GABAA antagonist) to determine whether it acts on GABAA receptor. Furthermore, MQAE assay was used to test the effect of ZER on the chloride ion concentration in cerebellar granule cells. ResultsCurrent data demonstrated that ZER dose-dependently (5–20 mg/kg) reduces the locomotor activity and sleep latency of mice, and extend sleeping time of mice. The results of ELISA showed that ZER increases the level of GABA/Glu in rats brain tissue, in particular in hypothalamus. Molecular docking results revealed that ZER has a strong affinity to GAD67 and Gephyrin protein. The Western blot and Immunohistochemistry data indicated that ZER up-regulates the expression of GAD67 and Gephyrin protein in rat’s hypothalamus. Antagonism test results demonstrated that flumazenil and bicuculline reverse the effect of ZER on threshold dose of pentobarbital sodium sleep experiments. In addition, ZER also could dose-dependently (5–20 μM) increase the chloride ion concentration in cerebellar granule cell, suggesting that ZER induces the opening of chloride channel, exerts central inhibitory effect. ConclusionZER has a significant sedative effect in mice and rat, and the effect is associated with GABAergic nervous system. The present results suggest that ZER, as one of the major bioactive ingredients of SP, contributes to the sedative effect and provide substantial evidence for its traditional use of anti-“Khii” in clinic of Syringa pinnatifolia.

Black pepper (Piper nigrum) fruit-based gold nanoparticles (BP-AuNPs): Synthesis, characterization, biological activities, and catalytic applications – A green approach

Abstract As compared to conventional techniques, currently nanotechnology has gained significant attention of scientists for the development of plant-based natural nanoparticles (NPs) due to their safety, effectiveness, and environment friendly nature. The current study was aimed for development, characterization (energy-dispersive X-ray, ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy), and evaluation of the biological efficiency of black pepper (BP; Piper nigrum) fruit-based gold NPs (BP-AuNPs) through different in vitro and in vivo assays. BP extract revealed maximum antibacterial and antifungal potential against Escherichia coli (24 mm) and Aspergillus flavus (47 mm), respectively. However, BP-AuNPs (200 µg·mL−1) inhibited the urease, xanthine oxidase, and carbonic acid-II activities with a percent inhibition of 83.11%, 91.28%, and 86.87%, respectively. Further, the anti-inflammatory effect of BP extract at the dose of 100 mg·kg−1 was 72.66%, whereas for BP-AuNPs it was noticed to be 91.93% at the dose of 10 mg·kg−1. Similarly, the extract of BP and prepared AuNPs demonstrated significant (p &lt; 0.01) sedative effect at all tested doses. The BP-AuNPs catalytically reduced methyl orange dye. Results suggest that BP-AuNPs possess significant biological activities, and further studies must be conducted to identify the probable mechanism of action associated with these activities.

Phytochemical and pharmacological investigation of the ethanol extract of Byttneria pilosa Roxb.

BackgroundTraditionally, the herb Byttneria pilosa Roxb. is used for bone fractures, boils, scabies, rheumatalgia, snake bites, syphilis, elephantiasis, poisoning, and eye infection. Scientific reports suggest that it has significant anti-inflammatory, analgesic, anti-diarrheal, anxiolytic, locomotion, sedative and anti-obesity effects. This study aims at the investigation of the phytochemical and pharmacological properties of the ethanol extract of this herb.MethodsFresh whole plant was extracted with absolute ethanol. A preliminary phytochemical investigation was followed by the evaluation of thrombolytic, anti-inflammatory, and anti-nociceptive activities by applying human clotted blood lysis, egg albumin, and acetic acid-induced writhing models, respectively.ResultsPhytochemical investigation suggests that B. pilosa possesses alkaloids, flavonoids, glycosides, terpenoids, tannins, saponins, and reducing sugars. The extract exhibited clot lysis and anti-inflammatory effects in a concentration-dependent manner. B. pilosa extract at 250 and 500 mg/kg also showed significant (p < 0.05) dose-dependent anti-nociceptive activity in Swiss albino mice.ConclusionThe B. pilosa ethanol extract contains many important secondary metabolites and has thrombolytic, anti-inflammatory, and anti-nociceptive activities. More research is necessary on this hopeful medicinal herb.

Neuro Pharmacological Effect of Cyclohexane 1, 2, 3, 4, 5, 6-Hexol and (2Z, 6E) 3, 7, 11-Trimethyldodeca-2, 6, 10-Trien-1-Ol , Isolated from Launaea Pinnatifida Cass in Mice

Cyclohexane 1,2,3,4,5 6-hexol and (2Z, 6e) 3,7, 11-trimethyldodeca-2, 6 10-trien-1-ol, isolated from Launaea Pinnatifida Cass were evaluated for their neuro pharmacological properties in mice in terms of analgesic and sedative effects. The compounds exhibited potent analgesic effect at the dose of 10 mg/kg in Eddy’s hot plate test similar to pentazocin, the standard drug. Significant sedative effect was exhibited by the test samples in mice, subjected to both the loco motor activity and marble burying activity compared with the standard drugs chlorpromazine and diazepam respectively at the dose of 10mg/kg. This study confirms at least partly the ancient use of Launaea Pinnatifida Cass as a medicine that cures neuro pharmacological disorders.

A comparative study to evaluate the efficacy of intraperitoneal instillation of 0.25% levobupivacaine with or without clonidine (0.75 μg/kg) for postoperative analgesia in patients undergoing laparoscopic cholecystectomy

Background: In recent years, the use of intraperitoneal instillation of local anesthetics with adjuvants has become popular for postoperative analgesia in laparoscopic cholecystectomy. This study aimed to compare the analgesic efficacy and safety of levobupivacaine alone or with clonidine as an adjuvant given through intraperitoneal instillation in laparoscopic cholecystectomy under general anesthesia.Material and Methods: In this prospective randomized double-blind study, 100 patients, aged 18–60 years belonging to ASA physical status I or II, were randomly allocated into two groups. Group L (n = 50) received 0.25% levobupivacaine 28 ml + 2 ml normal saline, whereas Group LC (n = 50) received 0.25% levobupivacaine 28 ml + clonidine 0.75 μg/kg (diluted in 2 ml normal saline) as intraperitoneal instillation before removing trocar. The duration of analgesia, pain scores, total number of doses, and amount of rescue analgesic consumed in 24 h, sedation score, hemodynamics, and adverse effects was noted.Results: Duration of analgesia was significantly prolonged in Group LC (744.10 ± 96.72 min) compared to Group L (525.20 ± 67.91 min) (P < 0.05). Pain scores (VAS) were significantly lower in Group LC (P < 0.05). The total number of doses and amount of rescue analgesic consumption in 24 hours were less in Group LC as compared to Group L (P < 0.05). Sedation, hemodynamics, and side effect profile were comparable in two groups (P > 0.05).Conclusion: Clonidine (0.75 μg/kg) was found to be a safe and effective adjuvant to 0.25% levobupivacaine for intraperitoneal instillation in laparoscopic cholecystectomy in terms of prolonged postoperative analgesia, lower pain scores, reduced rescue analgesic consumption along with no significant sedation, hemodynamic changes, and adverse effects.

Green Synthesis of Gold Nanoparticles Using Extract of Pistacia chinensis and Their In Vitro and In Vivo Biological Activities

The synthesis of metal nanoparticles by using plant extracts is previously explored in phytomedicines. Nanobiotechnology has many applications, including cosmetic, packing, coating, biomedicine, and enhanced biological activity. Keeping in view the importance of Pistacia chinensis, its gold nanoparticles (AuNPs) have been synthesized by the eco‐friendless and cost‐effective method. In this study, the synthesized nanoparticles were characterized by advanced techniques such as UV‐visible spectroscopy, Fourier transform infrared (FT‐IR), and atomic force microscope (AFM) analysis. The biological activities of these synthesized nanoparticles were examined in vitro by measuring the enzymatic inhibition potential on urease and carbonic anhydrase and in vivo by determining the analgesic and sedative activities. The UV spectrum indicated various peaks at the range of 530‐550 nm, showing nanoparticles formation. The FT‐IR spectroscopy of the extracts and AuNPs indicated the presence of NH, C═N, and N═O in the extract involved in the nanoparticles synthesis. The size of nanoparticles was determined by AFM analysis. The AFM showed that the nanoparticles range from 10 to 100 nm and are almost spherical in shape. The synthesized AuNPs exhibited significant urease inhibition potential with an IC50 value of 44.98. Similarly, the nanoparticles exhibited good carbonic anhydrase inhibition with an IC50 value of 53.54 against acetazolamide having IC50 0.13. Pistacia chinensis extract and its AuNPs exhibited excellent attenuation p &lt; 0.01 in acetic acid‐induced writhing model at a dose of 15 mg/kg. The synthesized nanoparticles showed a significant sedative effect p &lt; 0.001 compared to the standard drug. This research work has developed a green method to synthesize nanoparticles by using Pistacia chinensis extract and directed the researcher to purify active phytochemicals from Pistacia chinensis involved in nanoparticles synthesized.

Punica granatum peel extracts mediated the green synthesis of gold nanoparticles and their detailed in vivo biological activities

Abstract Requirements for developing new methodologies to biosynthesize nanoparticles are increasing day by day. The typical chemical synthesis of nanoparticles has raised concerns regarding environmental safety and adverse impact on human health. Therefore, there is an urgent need to develop green synthesized nanoparticles that are considered to be safe, ecofriendly, and cost-effective as compared to chemical approaches. Hence, in this study, we synthesized and characterized pomegranate peel extract-based gold nanoparticles (PP-AuNPs) through UV-visible spectroscopy, FT-IR, and AFM microscopy. Furthermore, the biological activities like analgesic, muscle relaxant, and sedative properties of synthesized PP-AuNPs were also determined. The change of color to dark ruby indicates the formation of AuNPs. The surface plasma resonance (SPR) peak in the absorption spectra was shown at 525 nm by using (UV-Vis) spectroscopy. A single distinctive peak implied the shape of nanoparticles to be spherical. AFM images revealed that the biosynthesized nanoparticles were spherical in shape. Furthermore, the images confirm the uniform distribution of PP-AuNPs with particle sizes ranging from 4 to 16 nm. Different classes of phytochemicals were preliminarily identified in extracts. The analgesic effect of extracts (70.04%) and PP-AuNPs (81.98%) demonstrated a significant (p &lt; 0.001) percent reduction in writhing at a dose of 100 and 15 mg·kg−1, respectively. A mild muscle relaxant effect was noted against both the tested samples while a significant sedative effect was observed for both samples; however, PP-AuNPs weres more sedative compared to the extract. Pomegranate peel extracts and synthesized PP-AuNPs were found to possess significant analgesic, muscle relaxant, and sedative properties.

The skeletal muscle relaxer cyclobenzaprine is a potent non‐competitive histamine H1 receptor antagonist

Cyclobenzaprine (Flexeril®) is a tricyclic dimethylpropanamine skeletal muscle relaxant that is used clinically to decrease muscle spasm and hypercontractility, without altering homeostatic muscle function. Although the absolute mechanism of action of cyclobenzaprine is unknown, it acts centrally to reduce tonic somatic motor function, likely via modulation of serotonergic and/or noradrenergic systems. While cyclobenzaprine is effective as a muscle relaxant, greater than 30% of patients experience drowsiness and sedative effects, yet, the mechanisms that cause these side effects are also undescribed. Based on this common adverse effect profile and the structural similarity of cyclobenzaprine to tricyclic antidepressants, we hypothesized that cyclobenzaprine facilitates sedative effects via off-target antagonism of central histamine H1 receptors (H1R). Here, for the first time, we present data that demonstrate that cyclobenzaprine exhibits low nanomolar affinity for the cloned human H1R, as well as that expressed in both rat and mouse brain. Using saturation binding experiments, our results demonstrate that cyclobenzaprine binds to the H1R in a non-competitive manner. Finally, using functional Ca+2 influx assays and novel TRUPATH BRET sensors, we show that cyclobenzaprine also blocks histamine-mediated H1R functional activity in a non-competitive manner. Given that cyclobenzaprine readily crosses the blood-brain barrier and its muscle relaxant effects occur centrally, our data suggest that off-target central antagonism of H1R by cyclobenzaprine facilitate the significant sedative effect of this agent seen in patients.

Synthesis, characterization, biological activities, and catalytic applications of alcoholic extract of saffron (Crocus sativus) flower stigma-based gold nanoparticles

AbstractCurrently, nanotechnology is gaining massive attention compared to conventional methods as the biosynthesis of plant-based nanoparticles is considered safe, effective, and ecofriendly. Therefore, keeping in view the importance of nanotechnology, the present study was designed to synthesize, characterize, and evaluate the biological effectiveness of saffron stigma-based gold nanoparticles (SS-AuNPs) for theirin vitroandin vivobiological properties. These gold nanoparticles were characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). The highest antibacterial effect was observed by the saffron extract againstEscherichia coli(22 mm). SS-AuNPs significantly inhibited the activity of enzyme urease (54.98%) and CA-II (64.29%). However, the nonsignificant inhibitory effect was observed in the case of α-chymotrypsin. Maximum analgesic (84.98%) and antiinflammatory (88.98%) effects were observed for SS-AuNPs (10 mg/kg). Similarly, SS-AuNPs demonstrated a significant (P&lt; 0.01) sedative effect at all tested doses.

In Vivo Anti-inflammatory, Analgesic, and Sedative Studies of the Extract and Naphthoquinone Isolated from Diospyros kaki (Persimmon)

Anti-inflammatory, analgesic, and sedative medicine is used with numerous side effects, including peptic ulcer, headache, addiction, and other complications. In this regard, discovery research is undergoing a process to discover effective, safe, and economical drugs with no side effects. The aim of this study was to assess chloroform extracts and isolated compounds for anti-inflammatory, analgesic, and sedative activities in animal models. The anti-inflammatory potential was measured by using the carrageenan-induced and histamine-induced paw edema procedure, while the analgesic potential was determined using a hot plate analgesiometer. The sedative effect was observed in an animal model for screening of the locomotor effect of the extract and isolated compound 1. Our data exhibited that the extract and compound 1 attenuated carrageenan-induced and histamine-induced paw edema (93.98 and 89.54%, respectively). Furthermore, compound 1 attenuated biphasic edema associated with histamine and prostaglandins. The chloroform extract showed a moderate analgesic effect; however, compound 1 showed a significant analgesic potential (p < 0.001) by increasing the latency time of the animals in the thermally induced algesia model. Compound 1 exhibited a significant sedative effect and dose-dependent analgesic activity. It is concluded that the chloroform extract and compound 1 showed remarkable anti-inflammatory, analgesic, and sedative activities. This research work strongly rationalizes the folkloric usage of Diospyros kaki in the treatment of inflammation, pain, and insomnia.

Sleep time and efficiency in patients undergoing laboratory-based polysomnography.

Sleep quality in patients studied with laboratory-based polysomnography may differ from sleep quality in patients studied at home but remains clinically relevant and important to describe. We assessed objective sleep quality and explored factors associated with poor sleep in patients undergoing laboratory-based polysomnography. We reviewed diagnostic polysomnography studies from a 10-year period at a single sleep center. Total sleep time (TST) and sleep efficiency (SE) were assessed as markers of sleep quality. Poor sleep was defined as TST ≤ 4 hours or SE ≤ 50%. Multivariable analysis was performed to determine associations between objective sleep quality as an outcome and multiple candidate predictors including age, sex, race, body mass index, comorbidities, severity of obstructive sleep apnea, and central nervous system medications. Among 4957 patients (age 53 ± 15 years), average TST and median SE were 5.8 hours and 79%, respectively. There were 556 (11%) and 406 (8%) patients who had poor sleep based on TST and SE, respectively. In multivariable analysis, those who were older (per 10 years: 1.48 [1.34, 1.63]), male (1.38 [1.14,1.68]), and had severe obstructive sleep apnea (1.76 [1.28, 2.43]) were more likely to have short sleep. Antidepressant use was associated with lower odds of short sleep (0.77 [0.59,1.00]). Older age (per 10 years: 1.48 [1.34, 1.62]), male sex (1.34 [1.07,1.68]), and severe obstructive sleep apnea (2.16 [1.47, 3.21]) were associated with higher odds of poor SE. We describe TST and SE from a single sleep center cohort. Multiple demographic characteristics were associated with poor objective sleep in patients during laboratory-based polysomnography. Harrison EI, Roth RH, Lobo JM, et al. Sleep time and efficiency in patients undergoing laboratory-based polysomnography. J Clin Sleep Med. 2021;17(8):1591-1598.