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В огляді літератури подані сучасні відомості щодо клінічної ефективності, безпеки та переносимості класичного представника другого покоління H1-антигістамінних препаратів дезлоратадину при лікуванні алергічного риніту в дітей. Для написання статті здійснювався пошук інформації з використанням баз даних Scopus, Web of Science, MedLine, PubMed, Google Scholar. Надана коротка характеристика фармакокінетики та фармакодинаміки дезлоратадину, що є потужним і селективним щодо H1-рецепторів зворотним агоністом із найтривалішим періодом напіврозпаду, який не проникає через гематоенцефалічний бар’єр і не має седативної дії. Акцентовано увагу на здатності дезлоратадину не тільки ефективно пригнічувати гістамінасоційовані клінічні прояви алергічного риніту, але й пригнічувати активність запального процесу за рахунок зниження активності фактора транскрипції NF-kB. У наукових дослідженнях показана висока ефективність дезлоратадину в купіруванні клінічних проявів алергічного риніту в дітей та вказано на хороший профіль безпеки під час його використання.

Background & objectives: Endoscopy is an invasive and painful procedure. The use of sedatives, especially in children, is expanding. The aim of this study was to compare the sedative effects of ketofol and the combination of midazolam-ketamine in upper endoscopy in children aged 1 to 14 years who referred to Taleghani Hospital in Gorgan. Methods: In this study, 55 children entered the study 1 to 14 years after obtaining parental consent. They were then divided into two groups, ketamine-propofol (KP) and ketamine-midazolam (KM), by simple randomization. At all stages of the work, patients underwent cardiac and respiratory monitoring. All hemodynamic parameters and ramsy sedation score (RSS) were recorded for all participants in the 5 time periods before, during and after endoscopy. ANOVA test and bonferroni tracking test were used in spss software to analyze and compare data. Results: 54.5% were male patients. The ANOVA test showed that the scores of the two groups at the time of the study had a statistically significant difference (p=0.02). In the KM group, the mean blood pressure and heart rate of patients increased at all times compared to before the intervention (p=0.005). Blood pressure in the KP group had a steady trend over time (p

Dexmedetomidine is a fairly new and promising drug for use in intensive care and surgery. Due to the fact that it is an agonist of alpha-2-adrenoceptors, dexmedetomidine has an analgesic, sedative effect and affects hemodynamic parameters. Due to the fact that dexmedetomedin does not have the ability to suppress respiration, it is used in patients with respiratory disorders. Dexmedetomidine has minimal side effects and a wide range of uses.

Aim: To analyse the effects of different propofol starting doses as premedication for endotracheal intubation on blood pressure in neonates. Methods: Neonates who received propofol starting doses of 1.0 mg/kg (n = 30), 1.5 mg/kg (n = 23) or 2.0 mg/kg (n = 26) as part of a previously published dose-finding study were included in this analysis. Blood pressure in the 3 dosing groups was analysed in the first 60 minutes after start of propofol. Results: Blood pressure declined after the start of propofol in all 3 dosing groups and was not restored 60 minutes after the start of propofol. The decline in blood pressure was highest in the 2.0 mg/kg dosing group. Blood pressure decline was mainly dependent on the initial propofol starting dose rather than the cumulative propofol dose. Conclusion: Propofol causes a dose-dependent profound and prolonged decrease in blood pressure. The use of propofol should be carefully considered. When using propofol, starting with a low dose and titrating according to sedative effect seems the safest strategy.

Background. The aim of the study is to evaluate the quality and safety of the sedative effect of anesthesia in ambulant ophthalmic surgery by using continuous intravenous infu­sion of Dexmedetomidine. Materials and Methods. Patients were randomized into groups by age (people from 65 to 75 years old, old age 76 years, middle age, young people, children), by gender (men, women). The physical status of patients was assessed using the ASA scale and the dynamics of vegetatic activity by the Kerdo index. Sedation was assessed using the Richmond Sedation Scale RASS.Results. It was found that the difference in the frequency of adverse effects of the appointment of Dexmedetomidine clearly confirms the need to adjust the dose of Dexmede­tomidine, depending on the state of the autonomic nervous system. The use of Dexmedetomidine according to the rec­ommendations made it possible to achieve a safe level of sedation and eliminate side effects in ambulant ophthalmic surgery.Conclusions: Parenteral continuous infusion of Dexmedetomidine pro­vides an effective level of sedation for ambulant ophthalmic surgery and maintaining patient­surgeon contact. Safety is confirmed by a low level of critical incidents, no respiratory depression at the target sedation level. The patency of the upper airways was better compared to previous experience with propofol., Цель исследования: оценить качество и безо­пасность седации при проведении анестезиологиче­ского обеспечения при амбулаторных операциях в оф­тальмохирургии, применяя непрерывную инфузию Дексмедетомидина.Материалы и методы. Пациенты были рандомизирова­ны на группы по возрасту (пожилые люди от 65 до 75 лет, старческий возраст 76 лет, дети, молодые люди, средний возраст), по полу (мужчины, женщины). Прово­дилась оценка физического статуса пациентов по шкале ASA и оценка динамики вегетативной активности по ве­гетативному индексу Кердо. Оценка уровня седации про­водилась по шкале возбуждения­седации Ричмонда RASS.Результаты исследования. Было показано, что разница в частоте неблагоприятных последствий назначения Дексмедетомидина наглядно подтверждает необходи­мость коррекции дозы Дексмедетомидина в зависимости от состояния автономной нервной системы. Использо­вание Дексмедетомидина согласно рекомендациям позво­ляло достичь безопасного уровня седации и устранения побочных эффектов в амбулаторной офтальмохирургии.Выводы: В/в непрерывная инфузия Дексмедетомидина обес­печивает эффективный уровень седации офтальмо­логических пациентов при амбулаторных операциях, сохраняя при этом контакт пациента с хирургом. Безопасность подтверждается низким уровнем критических инцидентов, отсутствующей депрессией дыхания при целевом уровне седации. Проходимость верхних дыхательных путей была лучшей по сравнению с предыдущим опытом использо­вания пропофола в качестве единственного седатив­ного средства., Мета дослідження: оцінити якість і безпечність седації при проведенні анестезіологічного за­безпечення при амбулаторних операціях в офтальмохірургії, застосовуючи безперервну внутрішньовенну інфузію ДексмедетомідинуМатеріали і методи: пацієнти були рандомізовані на групи за віком (літні люди від 65 до 75 років, старечий вік 76 років, діти, молоді люди, середній вік), за статтю (чоловіки, жінки). Проводилась оцінка фізичного статусу пацієнтів за шкалою ASA та оцінка динаміки вегетативної активності за вегетативним індек­сом Кердо. Оцінка рівня седації проводилась за шкалою збудження­седації Річмонда RASS.Результати дослідження. Було показано, що різниця в частоті несприятливих наслідків призначення Дексмедетомідину наочно підтверджує необхідність корекції дози Дексмедетомідину залежно від стану автономної нервової системи. Використання Дексмедетомідину згідно з рекомендаціями дозволяло досяг­ти безпечного рівня седації й усунення побічних ефектів в амбулаторній офтальмохірургії.Висновки: В/в безперервна інфузія Дексмедетомідину забезпечує ефективний рівень седації офтальмологічних паці­єнтів при амбулаторних операціях, зберігає при цьому контакт пацієнта з хірургом. Безпека підтверджується низьким рівнем критичних інцидентів, відсутньою депресією дихання при ці­льовому рівні седації. Прохідність верхніх дихальних шляхів була кращою порівняно з попереднім досвідом використання Про­пофолу в якості єдиного седативного засобу.

Allergic rhinitis (AR) is the most common undiagnosed chronic condition in children. Moderate/severe AR symptoms significantly impair quality of life, and cause sleep disruption, absenteeism and decreased productivity. Additionally, untreated AR predisposes children to asthma and other chronic conditions. Although intranasal corticosteroids are the most effective pharmacologic treatment for AR, oral antihistamines are often preferred. First-generation antihistamines may be chosen to relieve AR symptoms as they are inexpensive and widely available; however, they cause sedative and cardiovascular negative effects due to poor receptor selectivity. Therefore, second-generation antihistamines were developed to reduce adverse effects while retaining efficacy. There are fewer clinical trials in children than adults, therefore, efficacy and safety data is limited, particularly in children under 6 years, highlighting the need to generate these data in young children with AR. Fexofenadine, a highly selective second-generation antihistamine, effectively alleviates symptoms of AR, is non-sedating due to decreased blood–brain barrier permeability, and is devoid of cardiovascular side effects. Importantly, fexofenadine relieves the ocular symptoms of allergic conjunctivitis, which occur concomitantly with AR, improving quality of life. Overall, fexofenadine displays a favorable safety profile and results in greater treatment satisfaction in children compared with other second-generation antihistamines. This review aimed to evaluate and compare the safety and efficacy of fexofenadine with other available first- and second-generation antihistamines in children with AR. Supplementary Information The online version contains supplementary material available at 10.1186/s13223-021-00614-6.

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH).Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated.Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased.Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

Herbal medicine is the oldest form of health care known to mankind. Medicinal plants can be important sources of unknown chemical substances with potential therapeutic effects. The study of plant species with diuretic effects is still a fruitful research in search of new diuretic and sedative drugs. The present study was carried out to evaluate the diuretic and sedative effect of ethanolic extract of Basella alba (BAE) in wistar rats & mice by using Lipschitz model and Rota rod model respectively. The urine volume, electrolyte levels in rats and fall of time of mices from rota rod were measured. BAE showed significant (p

Chromolaena odorata (L.) R.M.King &amp, H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABAA receptor antagonist, reversed its effects. It was especially interesting to note that β-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.

To explore the effect of midazolam in the treatment of senile acute cerebral infarction is the main objective. the patients were divided into observation group (n=55) and control group (n=55) by envelope method, the control group was given routine treatment, the observation group was given midazolam on the basis of the control group, the time required for sedation, mean arterial pressure, heart rate and so on were observed. There was no significant difference in sedation time between the observation group and the control group (p>0.05). The awakening time of the observation group was (8.10±1.54) min, which was significantly shorter than that of the control group (p

Aim There are no definitive data to determine whether age influences the effects of dexmedetomidine (DEX) treatment. Thus, we investigated whether older age was associated with more favorable sedative action by DEX in sepsis patients who required mechanical ventilation. Methods This study involved a post-hoc analysis of data from the Dexmedetomidine for Sepsis in the ICU Randomized Evaluation (DESIRE) trial. The patients were categorized based on median age into elderly and younger groups. The two groups were then compared during the first 7 days after ventilation based on proportion of patients with well-controlled sedation (Richmond Agitation-Sedation Scale score between -3 and +1), days free from delirium (based on the Confusion Assessment Method for ICU), and days free from coma (Richmond Agitation-Sedation Scale score between -4 and -5). Results One hundred and one patients were assigned to the elderly group and 100 patients were assigned to the younger group. In the elderly group, 50 patients received DEX treatment and 51 patients received non-DEX treatment, with the DEX arm having significantly better-controlled sedation (range, 14-52% versus 16-27%; P = 0.01). In the younger group, 50 patients received DEX treatment and 50 patients received non-DEX treatment, with no significant difference in the proportions of well-controlled sedation (range, 20-64% versus 24-60%; P = 0.73). There were no significant differences in the numbers of days free from delirium or coma between the groups. Conclusion In elderly sepsis patients who require ventilation, dexmedetomidine could be more effective than other sedative agents for achieving proper sedation.

ObjectiveDexmedetomidine has a good sedative effect and does not affect the judgment of the patient's consciousness level. However, its effectiveness for sedation and cerebral protection after craniotomy in hypertensive intracerebral hemorrhage (HICH) patients is unknown.MethodsA retrospective study of 164 postoperative HICH patients who underwent sedation with dexmedetomidine or midazolam was conducted. The Ramsay sedation score, mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SpO2), and respiratory rate were measured at the indicated time points. Human soluble protein-100β (S-100β) and neuron-specific enolase (NSE) levels were also compared between the two groups.ResultsDexmedetomidine treatment showed a significantly better effect than midazolam on decreasing the frequency of apparent agitation. The MAP and HR, but not the SpO2,were significantly decreased and lower than those in midazolam group. Detection of plasma S-100β and NSE proteins revealed a significant decrease in the dexmedetomidine group compared with the midazolam group. The 6-month follow-up evaluation indicated a significantly better prognosis of postoperative HICH patients treated with dexmedetomidine than for those treated with midazolam.ConclusionsDexmedetomidine is effective for sedation in postoperative HICH patients and may be beneficial for their outcome.

Background: Dexmedetomidine has a mild sedative effect and may reduce mortality in mechanically ventilated critically ill patients. However, few studies have examined the effects of dexmedetomidine in patients with sepsis who require mechanical ventilation. The aim of this study was to investigate the association between dexmedetomidine and mortality in patients with sepsis requiring mechanical ventilation, using a nationwide inpatient database in Japan. Methods: Using the Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2016, we identified adult patients with sepsis who required mechanical ventilation for more than 2 days. Patients were divided into those who received dexmedetomidine and those who received midazolam or propofol within 1 day after admission. Logistic regression analysis, propensity score-matched analysis, and instrumental variable analysis were performed to compare all-cause 28-day mortality and duration of mechanical ventilation between the groups. Results: In total, 50 671 were eligible patients, including dexmedetomidine group (n = 13 759) and propofol or midazolam group (n = 36 912). The dexmedetomidine group had significantly lower all-cause 28-day mortality compared with the group receiving midazolam or propofol, as shown by the logistic regression analysis (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.73-0.84), the propensity score–matched analysis (OR: 0.85; 95% CI: 0.80-0.91), and the instrumental variable analysis (OR: 0.64; 95% CI: 0.57-0.73). The duration of mechanical ventilation in the dexmedetomidine group was significantly shorter than that in the midazolam or propofol group. Conclusions: Dexmedetomidine was associated with a reduction in all-cause 28-day mortality and duration of mechanical ventilation.

BACKGROUND Epidural anaesthesia is widely accepted for lower limb surgery in terms of avoidance of laryngoscopic surge, better perioperative pain management, greater patient satisfaction and attenuation of neuroendocrine response to surgery. Among many drugs, α₂- adrenergic agonist has been used widely as an adjuvant to local anaesthetics due to its better analgesic and sedative property without significant respiratory depression. The aim of this study was to compare the analgesic and sedative effects of dexmedetomidine and clonidine in epidural anaesthesia. MATERIALS AND METHODS 86 patients of either sex aged 40-65 years and body weight of 40-70 Kgs of ASA class I-II, posted for elective lower limb orthopaedic surgeries were randomly allocated in two equal groups either to have 0.75% ropivacaine and dexmedetomidine (group RD) or 0.75% ropivacaine and clonidine (group RC) and were observed regarding block characteristics in term of onset and duration for maximum sensory level achieved, time to complete motor block ,intraoperative and postoperative sedation level, time to two segment regression of sensory block, time to first analgesic requirement, hemodynamic stability and adverse effects. Postoperative epidural top-up dose of 8 ml 0.2% ropivacaine was used as rescue analgesia. Observed data were tabulated in the Excel sheet and analysed with SPSS for windows (Version 12.0). Categorical data are presented as percentage of number of patients [n (%)]; continuous data are expressed as mean ± SD. Statistical analysis was done using independent samples t test (continuous data) and Chi-square test (Categorical data). A ‘p’ value

Quantitative contrast-enhanced ultrasonography (CEUS) enables non-invasive and objective evaluation of intestinal perfusion by quantifying the intensity of enhancement on the intestine after microbubble contrast administration. During CEUS scanning, sedation is sometimes necessary to maintain animal cooperation. Nevertheless, the effect of sedative administration on the canine intestinal CEUS is unknown. This study aimed to investigate the effect of sedation with a combination of butorphanol and midazolam on the duodenal CEUS-derived perfusion parameters of healthy dogs. For this purpose, duodenum was imaged following contrast administration (Sonazoid®, 0.01 ml/kg) in six healthy beagles before and after intravenous injection of a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg). Furthermore, hemodynamic parameters including blood pressure and heart rate were recorded during the procedure. Five CEUS derived perfusion parameters including time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), wash-in and wash-out rates (WiR and WoR, respectively) before and after sedation were statistically compared. The result showed that no significant change was detected in any of perfusion parameters. Systolic and mean arterial pressures significantly reduced after sedative administration, but diastolic arterial pressure and heart rate did not significantly change. Moreover, no significant partial correlation was observed between perfusion parameters and hemodynamic parameters. Thus, we concluded that the combination did not cause significant influence in duodenal CEUS perfusion parameters and could be a good option for sedation prior to duodenal CEUS in debilitated dogs.

Sedation can be defined as the use of sedative medication to relieve intolerable and refractory distress by reducing patient consciousness. Sedation can cause mild depression in the central nervous system without loss of consciousness and calming effect and prevent seizures. Cherry is a plant with sedative potential effect, contain melatonin as a flavonoid compound. This study aims to determine sedative effect, effective dose, and sleep duration in white mice male after cherry juice administration. The rotarod test was conducted to determine the resistance time of tested mice on a rotating rod. The observed parameter was the length of the time the mice running on a rotating rod at a speed of 28 rpm. Cherry juice was prepared using a juicer and then filtered with muslin cloth and dried with vacuum dryer. Cherry juice was prepared in 3 doses, they were treatment dose 1, 2, and 3 with cherry juice of 8.3, 16.6, and 25 mg/20gBW, respectively. Aquadest was used as negative control (0.5 ml/ mice), while phenobarbital was the positive control at a dose of 0.8 mg/ 20gBW). The results showed that treatment dose 3 containing 25 mg/20gBW) cherry juice was the most effective dose with the fastest falling effect (13.41 second) on rotarod and the longest duration of sleep time (45.92 minute).

Background: Besides effect of general anesthesia, sevoflurane also induces hyperactivity during induction and recovery, especially in young children. Lack of satisfied animal model impedes the investigation of causes of the hyperactivity as well as its prevention. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker might produce sedative effect. This study developed a novel mice model of hyperactive behaviors and further explored effects of HCN channel blocker on sevoflurane-induced hyperactivity. Methods: C57BL/6 mice were used in the present study. Maximal speed, mean speed, total movement distance and resting percentage of mice were quantitatively measured by behavioral tracking software. Age-dependence of this model was also analyzed. HCN channel blocker ZD7288 at doses of 6.25 and 12.5 μg/kg were intraperitoneal injected to prevent sevoflurane-induced hyperactivity. Results: In the behavioral model, sevoflurane could induce significant hyperactivity in mice under 1% sevoflurane inhalation and in recovery period, characterized as increased movement speed and total distance. The sevoflurane-induced hyperactivity was more significant in young mice than adult (P

Schisandra chinensis is a traditional Chinese medicine that has been used for treating insomnia and neurasthenia for centuries. Lignans, which are considered to be the bioactive components, are apt to be extracted by supercritical carbon dioxide. This study was conducted to investigate the sedative and hypnotic activities of the supercritical carbon dioxide fluid extraction of S. chinensis (SFES) in mice and the possible mechanisms. SFES exhibited an obvious sedative effect on shortening the locomotor activity in mice in a dose-dependent (10–200 mg/kg) manner. SFES (50 mg/kg, 100 mg/kg, and 200 mg/kg, intragstrically) showed a strong hypnotic effect in synergy with pentobarbital in mouse sleep, and reversal of insomnia induced by caffeine, p- chlorophenylalanine and flumazenil by decreasing sleep latency, sleep recovery, and increasing sleeping time. In addition, it produced a synergistic effect with 5-hydroxytryptophan (2.5 mg/kg, intraperitoneally). The behavioral pharmacological results suggest that SFES has significant sedative and hypnotic activities, and the mechanisms might be relevant to the serotonergic and γ -aminobutyric acid (GABA)ergic system.

The analgesic, anti-inflammatory, anticonvulsant and CNS activities of the ethanolic extract of Butea monosperma roots were examined. The extract produced no significant inhibition of abdominal constrictions caused by acetic acid. It showed significant inhibition of the earlyphase of formalin-induced pain, also reduced the weight of granuloma induced by a cotton pellet. Moreover, the extract caused a moderate inhibition of ear swelling in mice caused by croton oil. In pentobarbital induced sleeping time test the extract slightly reduced the onset and increased the duration of sleeping. Therefore, Butea monosperma showed analgesic, antiinflammatory, mild anticonvulsant activities as well as sedative effect on CNS.Jahangirnagar University J. Biol. Sci. 4(1): 9-18, 2015 (June)

Background Solidago chilensis (syn. microglossa) is a plant from the Asteraceae family widely distributed in South America and used to treat inflammatory diseases. In 2009, it was listed as one of the native medicinal herbal plants used in the Brazilian public health system. In addition to its anti-inflammatory properties, a recent clinical study has shown antinociceptive effects of S. chilensis, introducing a new potential medical use for this plant. The aim of the present study was to investigate the antinociceptive activity of the hydroalcoholic extract of Solidago chilensis (HESc) in rodent models of pain. Methods The dried plant extract was obtained from its aerial parts, maintained in ethanol (100 g/l) and filtered. Rats or mice were treated with intraperitoneal injections of HESc (3, 10 or 30 mg/kg) 30 min before being submitted to writhing, 0.2%-formaline or hot-plate tests or prostaglandin E2 (PGE2) administration in the hind paw. Mechanical hypernociception and motor impairment were evaluated by electronic von Frey and rota-rod, respectively. Results HESc dose-dependently inhibited abdominal contortions in the writhing test and attenuated phases I and II formalin-induced nociceptive behavior. Treatment with HESc also increased thermal threshold and decreased PGE2-induced hypernociception without promoting motor impairment. Conclusions Our data suggest that, when systemically administered, HESc decreases nociception without inducing a sedative effect. Importantly, this effect was observed in both inflammatory and non-inflammatory models of pain and nociception, suggesting a specific non-inflammatory mechanism of HESc on pain. Our findings indicate that S. chilensis might be an important adjuvant in pain management.

Aim. The “PARUS” program included investigation of the analgesic, muscle relaxant and sedative effects of Mydocalm-Richter which acts as central muscle relaxant in patients with myofascial pain syndrome, taking into account its registered indication for use - the hypertonus and cross-striated muscle spasm. Materials and methods. Fifty patients with myofascial trigger points, the mean age of 41.67±11.86 years, have been enrolled in the study. All patients had undergone clinical examination that allowed the diagnosis of myofascial pain syndrome. The intensity of pain syndrome was evaluated using the pain visual analogue scales and McGill pain questionnaire. Visualization of area in spasm and evaluation of blood circulation was carried out using the ultrasound scan of target muscle. In order to objectively evaluate any conceivable hypotensive and sedative effects of Mydocalm-Richter we used the orthostatic test, Schulte’s test for attention span and perfor-mance distribution and Munsterberg’s test for attention discrimination and concentration. Results. The analgesic and muscle relaxant effects of Mydocalm-Richter become apparent by day 3 post-injection, and the muscle relaxation effect is reaching its maximum on day 10 post-injection. Cardiovascular function following administration of Mydocalm-Richter was evaluated using the orthostatic test which revealed good orthostatic tolerance. Single injection of tolperisone hydrochloride possessing a central muscle relaxant activity has no sedative effect and does not influence patient response time. The ultrasound examination data demonstrated the improvement and in some cases restoration of blood circulation in the myofascial trigger points. Conclusion. Clinical study “PARUS” conducted in patients with myofascial pain has demonstrated a positive muscle relaxant and analgesic effect of Mydocalm-Richter that resulted in restoration of peripheral circulation in the myofascial trigger pointsconfirmed by ultrasound examination. An important benefit of this drug product is the absence of sedative effect and arterial hypotension.

Epilepsy is a common clinical syndrome characterized by sudden and recurrent attacks and temporary central nervous system dysfunction caused by excessive discharge of neurons in the brain. Amber, a fossilized organic substance formed by the resins of conifers and leguminous plants, was prescribed to tranquilize the mind in China. In this paper, the antiepileptic effect of amber was evaluated by a pentylenetetrazole (PTZ)-induced epileptic model. An untargeted metabolomics approach was applied to investigate metabolic changes in the epileptic model, which was based on HILIC-UHPLC-MS/MS multivariate statistical analysis and metabolism network analysis. The outcome of this study suggested that 35 endogenous metabolites showed marked perturbations. Moreover, four metabolism pathways were mainly involved in epilepsy. After treatment by amber, the endogenous metabolites had a marked tendency to revert back to the situation of the control group which was consistent with phenobarbital. This study characterized the pentylenetetrazole-induced epileptic model and provided new evidence for the sedative effect of amber.

New diamino derivatives of pyrano[3,4-c]pyridines were synthesized by the pyridine ring recyclization. The presence of the intramolecular hydrogen bond in 6-[(4-methoxyphenyl)amino]-3,3-dimethyl8-methylamino-3,4-dihydro-1H-pyrano[3,4-c]pyridin-5-carbonitrile was identified by X-ray diffraction. A pharmacological study of the synthesized compounds was carried out in known tests, such as assay for antagonism induced by corazole subcutaneous injection and the open field test. The method of rotating rod was used to evaluate neurotoxicity. The diamino derivatives of pyrano[3,4-c]pyridines were found to possess neutrotropic properties. The synthesized compounds, as well as diazepam, prevent the occurrence of clonic seizures and clonic corazoleinduced convulsions in animals; however, they cause a behavior-depressing sedative effect.

Herein we report the synthesis of several new condensed furo[2,3-b]pyridines 3 from the 3-oxo derivatives of cyclopenta[c]pyridine, of 5,6,7,8-tetrahydroisoquinoline and of pyrano[3,4-c]pyridine 1. The obtained furo[2,3-b]pyridines 3 were used as starting materials for the synthesis of pyridofuropyrrolo[1,2-a]pyrimidines 4 and of pyridofuropyrimido[1,2-a]azepines 5. Interestingly enough, derivatives of pyridofuropyrimido[1,2-a]azepines 5 exhibited anticonvulsant activity significantly better than that of the commercial drug ethosuximide (zarontin). Some of them showed a sedative effect, unlike ethosuximide.

We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a β-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine.

The sedative effects of intramuscular (IM) alfaxalone in 2-hydroxypropyl-beta-cyclodextrin (alfaxalone-HPCD) were evaluated in cats. The cats were treated with alfaxalone-HPCD in five occasions with a minimum 14-day interval between treatments: an IM injection of 1.0 mg/kg (IM1), 2.5 mg/kg (IM2.5), 5 mg/kg (IM5) or 10 mg/kg (IM10), or an intravenous injection of 5 mg/kg (IV5). The sedative effects were evaluated subjectively using a composite measurement scoring system (a maximum score of 16). Cardio-respiratory variables were measured non-invasively. The median sedation scores peaked at 10 min (score 9), 15 min (score 14), 10 min (score 16), 10 to 20 min (score 16) and 2 to 5 min (score 16) after the IM1, IM2.5, IM5, IM10 and IV5 treatments, respectively. The IM5 treatment produced longer lasting sedation, compared to the IV5 treatment. Durations of maintenance of lateral recumbency after the IM10 treatment (115 ± 22 min) were longer than those after the IM2.5 (40 ± 15 min), IM5 (76 ± 21 min) and IV5 treatments (50 ± 5 min). Cardio-respiratory variables remained within clinically acceptable ranges, except for each one cat that showed hypotension (

We previously reported finding anxiolytic-like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)-α-santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)-α-santalol by inhalation or intraperitoneal injection, we assessed anxiolytic-like and locomotor activities using elevated-plus maze tests. We also examined the relationship between the emotional behavior and the (+)-α-santalol brain concentration. Anxiolytic-like activity was not observed immediately after administration or after water-immersion stress for 24 h for either the (+)-α-santalol 2 μL/L air inhalation or the (+)-α-santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)-α-santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water-immersion stress for 24 h. The brain (+)-α-santalol concentration was 2.6 µg/g tissue after (+)-α-santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)-α-santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic-like activity. Copyright © 2015 John Wiley & Sons, Ltd.

Objective To evaluate the effect of the peripherally acting α2-adrenoceptor antagonist vatinoxan (MK-467) on the sedative properties of medetomidine (MED) when injected intramuscularly (IM) in the same syringe and on reversal of this sedation with atipamezole in sheep. Study design Randomized, blinded, crossover experimental trial. Animals Eight healthy adult female sheep. Methods Sheep received MED (30 μg kg–1 IM) alone or combined in the same syringe with vatinoxan (300 μg kg–1 IM, MED+VAT) with a 2 week washout period. Atipamezole (150 μg kg–1 IM) was administered 30 minutes later for reversal. Sedation was assessed using two sedation scores, a visual analog score and a descriptive scale before treatments (T0) and at intervals up to 5 hours thereafter. Pulse rate (PR) was counted at T0 and at 30 (T30) and 90 (T90) minutes. Rectal temperature was measured at T0 and T90 postinjection. Plasma samples were analyzed for drug concentrations at T30 and T90. Results The first signs of sedation were seen significantly earlier after MED+VAT (4.6 ± 1.7 minutes versus 9.4 ± 2.6 minutes after MED) and the sedation scores were significantly higher after MED+VAT than MED. All animals laid with head down 10.0 ± 3.4 minutes after MED+VAT, whereas three MED animals did not become recumbent before atipamezole was administered. The plasma concentrations of dexmedetomidine were significantly higher at T30 (2.47 ± 0.2 ng mL–1) and significantly lower at T90 (1.23 ± 0.3 ng mL–1) with MED+VAT than with MED (1.19 ± 0.8 and 1.83 ± 0.4 ng mL–1, respectively). While no significant differences were observed between treatments in PR at T30, PR at T90 was significantly higher with MED+VAT than with MED. Conclusions and clinical relevance When administered IM in the same syringe, vatinoxan hastened and intensified the initial sedative effects of MED and enhanced the sedation reversal by atipamezole.

Maternal behavior is a highly motivated and well-organized social behavior. Previous studies have reported that anticonvulsants are frequently used in postpartum bipolar disorder. However, the maternal disruptive effect of the anticonvulsants has not been explored. The purpose of the present study was to examine the effect of anticonvulsants lamotrigine and riluzole on maternal behavior in postpartum female rats. On postpartum Day 3, Sprague-Dawley mother rats were given a single intraperitoneal injection of vehicle, lamotrigine (15, 25, 35 mg/kg), or riluzole (2, 4, 8 mg/kg). Maternal behavior was tested 30 min before and after injection. Animals treated with lamotrigine or riluzole had a longer pup retrieval latency, retrieved fewer pups into the nest, spent less time on nursing pups, as well as on building the disturbed nest, and animals treated with riluzole spent less time on pup licking. Whereas, the drugs in the tested doses did not shorten the total duration of behavior unrelated to maternal behavior. Overall, these data indicate that lamotrigine and riluzole disrupt major components of maternal behavior in postpartum female rats, but do not inhibit the behaviors unrelated to maternal behavior, which indicates that the maternal disruptive effect is not due to nonspecific sedative effect.

Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics.

Purpose It is reported that the sympathetic nervous system may play an important role in the arousal response. The present study evaluated the effect of stellate ganglion block (SGB) on electroencephalogram (EEG) activity in rats. Materials and methods Adult male Sprague–Dawley rats were divided into two groups: SGB (n = 10) or intramuscular (IM, n = 10) injection was performed with 0.2 ml 0.25 % bupivacaine. The spectral edge frequency 95 % (SEF 95 %), median frequency (MF), beta to theta ratio (BTR), and beta to delta ratio (BDR) were estimated 30 min before bupivacaine injection and 15, 20, 25, 30, 45, 55, and 100 min after SGB or IM injection. Results Ipsilateral ptosis occurred in all the rats that underwent SGB but did not occur in the IM group. Significant decrease of the 95 % SEF value, MF, BTR, and BDR was observed from 15 to 45 min after SGB compared with those of the IM group, respectively (p \ 0.05). Conclusions SGB with 0.2 ml 0.25 % bupivacaine significantly decreased EEG activities in rats. These results suggest that SGB can induce a sedative effect in rats. Further studies are required to investigate the behavioral tests for sedative effects of SGB.

The aims of this study were to assess the plasma concentrations of romifidine in horses after intravenous injection, to evaluate the red blood cell (RBC) partitioning of the anaesthetic drug, and to improve knowledge regarding its sedative effect in horses describing the pharmacokinetic model. Eight adult Standardbred horses received a single bolus of romifidine at a dosage of 100 μg/kg. Blood samples (5 mL) were collected immediately before romifidine administration (t 0), and at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 min after injection. A sedation score was recorded at the same time. The romifidine concentrations in plasma and red blood cells were determined by high performance liquid chromatography (HPLC). The plasma and red blood cell concentrations were correlated with the sedation at each time point. Romifidine produced a satisfactory level of sedation in all animals. The sedation was detectable in all horses for up to 105 min. All the animals returned to normal without any behavioural changes at 180 min. The romifidine concentrations in the red blood cells were significantly higher (P

To shed light on the role of central oxytocin (OXT) in regulating social behavior in cattle, the impact of intracerebroventricularly administered OXT agonist, carbetocin (CBT), on the social behavior of a group of familiar steers was investigated. In the first experiment, we determined the dose response of intracerebroventricularly administered CBT (0.5, 5 or 50 nmol) on plasma cortisol level and behavior using 7 steers aged from 6 to 10 months. Five of the steers were assigned to the second experiment. CBT (50 or 200 nmol/200 μl) in artificial cerebrospinal fluid (aCSF) or aCSF (200 μl) was injected into the third ventricle. Immediately after the injection, the animal and two peers were taken outside to the adjacent paddock. Thirty minutes later, maintenance and social behaviors of the animal were observed for 2 hr. CBT had no effect either on the basal cortisol level or on the maintenance and the abnormal behavior in steers with their movement restricted by a stanchion stall in the first experiment. However, in the same steers with no movement restrictions in the second experiment, CBT facilitated lying, probably because of its sedative effect via OXT receptor activation, which disturbed some aspects of social behavior. These results suggest that central OXT receptor activation might not affect social behavior itself among "familiar members", because the stimulation of the central OXT system by intracerebroventricular administration of CBT did not facilitate social behavior between familiar steers.

Fospropofol (fospropofol disodium), a sedative/hypnotic agent, is a water-soluble prodrug of propofol, metabolized in vivo to produce liberated propofol (producing the sedative effect), phosphate and formaldehyde. Intravenous fospropofol 6.5 mg/kg was significantly more effective than fospropofol 2.0 mg/kg (a placebo surrogate) as sedation in patients undergoing colonoscopy or flexible bronchoscopy, with regard to the primary endpoint of sedation success rate in randomized, double-blind, phase III trials. In patients undergoing colonoscopy, the sedation success rate was3-fold higher among fospropofol 6.5 mg/kg (n = 158) than fospropofol 2.0 mg/kg recipients (n = 102). Similar results were observed in patients undergoing flexible bronchoscopy; the sedation success rate was3-fold greater among fospropofol 6.5 mg/kg (n = 150) than among fospropofol 2.0 mg/kg recipients (n = 102). Fospropofol was generally well tolerated in clinical trials. Adverse events were mostly of mild to moderate severity, and were transient and self-limiting. Patients undergoing flexible bronchoscopy appeared to have a higher rate of sedation-related adverse events requiring airway assistance than did those undergoing colonoscopy or minor procedures.

BACKGROUND Delta9-tetrahydrocannabinol (Delta9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of Delta9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between Delta9-THC and propofol in terms of sedation and analgesia. METHODS Sedation was monitored by a rota-rod and analgesia by tail-flick latencies. Twenty mice received intraperitoneal injections of 50 mg/kg Delta9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with Delta9-THC and thiopental or Intralipid. RESULTS Injection of 50 mg/kg propofol caused a rapid onset of sedation with a minimum of 24 s on the rota-rod. Fifty mg/kg Delta9-THC alone had no sedative effects. Administration of Delta9-THC significantly reduced the sedative effect of propofol to at least 60 s on the rota-rod (P < 0.001). After increasing the propofol dose to 100 mg/kg in the presence of Delta9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of Delta9-THC. CONCLUSION The results indicate a dose-dependent antagonistic interaction between Delta9-THC and propofol, and also between Delta9-THC and thiopental.

The behavioral assessment of pain is essential for the analysis of pain mechanisms and the evaluation of analgesic drugs. The formalin test is one of such methods widely used as a model of injury-induced pain in rodents. This test is manually demanding and the recording of results is left to the subjectivity of the experimenters. Thus we developed a novel automated method to estimate the pharmacological response in formalin-induced licking behavior in rats using a multicolor detection technique. Two color markers were preliminarily applied to rats-yellow dye on the mouth and fluorescent green tape on the right hind paw. Behaviors of the animals were recorded from both above and below the subject, by a dual-view digital video camera system. After injection with formalin into the hind paw, rats exhibited a biphasic display of licking behavior. Licking time was measured by the sum of frames where the distance between these markers was less than an appropriate threshold of distance (TD). The split-plot analysis of variance demonstrated that the sum of squares of differences in licking time between manual and automated measurement was minimized when TD = 20mm. In addition, frames in which moving velocity of these markers is less than 2.5mm/s was neglected for calculation in order to eliminate sedative effect on the recorded data. On these conditions, subcutaneous administration of morphine in rats dose-dependently decreased formalin-elicited nociceptive responses. These results suggest that under optimal conditions the automated technique when applied to pharmacological studies are more reliable and efficient than if they are manually recorded.

Emergence agitation can occur following recovery from general anaesthesia. The patient may exhibit aggressive behaviour, disorientation, agitation and restlessness. Untreated, this complication may result in significant morbidity. We report two cases where droperidol was successfully used in the management of severe emergence agitation. In the first case, droperidol was administered to prevent the occurrence of postoperative agitation in a patient known to suffer from this condition following previous general anaesthetics. In the second case, droperidol was used to treat emergence agitation in a morbidly obese patient with a difficult airway who was aggressive and difficult to restrain. Both of these patients remained calm and co-operative, with stable cardio-respiratory parameters, following the administration of droperidol and showed no further signs of agitation. We suggest that droperidol is an effective medication that may be used to prevent and treat severe emergence agitation due to its rapid sedative effect and minimal cardio-respiratory depression.

Purpose: To determine the clinical sedative effect and dosage of intranasal midazolam in refraction and fundus examination of children with strabismus. Patients and Methods: Refraction and fundus examination with (n = 28) and without (n = 24) sedation were performed in 52 children with strabismus whose ages ranged from 7 to 26 months. We delivered a 5-mg/mL solution of midazolam via a syringe for 60 seconds to provide a dose of 0.2 mg/kg. We repeated the dose to a maximum of 0.3 mg/kg if there was no clinical sedative response after 10 to 15 minutes. The ease of examination and sedation for each patient was scored by a blinded observer. The groups were evaluated for ease of examination and the time needed to complete it. Results: We obtained clinically adequate sedation at a mean (± standard deviation) of 15 minutes (± 2.69 minutes). Sedation was achieved with a mean dose of 2.64 mg/kg (± 0.66 mg/kg). Children receiving midazolam had significantly calmer examination scores. The time needed to complete the examination was statistically significantly shorter for these children than for children not receiving sedation ( P < .05). Conclusions: Intranasal midazolam is a beneficial drug and method of delivery for the sedation of anxious children with strabismus undergoing refraction and fundus examination. Sedation prior to examination is effective in reducing the anxiety and time associated with ophthalmologic examination of children with strabismus. J Pediatr Ophthalmol Strabismus 2005;42:355–359.

Loperamide-induced suppressive effects on central nervous system closely relate to a lack of or decline in the P-glycoprotein (P-gp) function. The aim of this study was to determine the loperamide-induced sedative effect quantitatively and to investigate possible alterations in the pharmacokinetics of digoxin, a substrate for P-gp, in Japanese subjects.Loperamide hydrochloride (2 mg) was administered orally to 26 subjects and the critical flicker-fusion frequency threshold (CFF) values were measured every 30 min separately by portable instrument. Further, digoxin (0.25 mg) was administered to 8 subjects, and the plasma concentration was determined.In five subjects who complained of drowsiness, the CFF values more remarkably decreased compared with those in the other subjects. The Tmax and mean residence time (MRT) values of digoxin pharmacokinetics in four subjects with drowsiness were significantly lower and Cmax was higher than those in four subjects with marginal effect. Moreover, there were good correlations between the CFF value-time profile and the Cmax, Tmax, and MRT of digoxin.The determination of the CFF value after oral administration of loperamide will be useful for evaluating varied P-gp function and for anticipating individual variations in the disposition of P-gp substrates in humans.

Antianxiety action of diterpene alkaloid songorine was studied using Vogel conflict test. Songorine in a dose of 0.25 mg/kg demonstrated high anxiolytic activity comparable to that of phenazepam and produced no sedative effect.

The relationship between the cerebral pharmacokinetics of diazepam and its active metabolites (desmethyldiazepam, oxazepam) and the anxiolytic effect evaluated by the four-plates test and the light/dark test were investigated after a single intra-peritoneal injection of diazepam (1 mg/kg or 1.5 mg/kg). For up to 30 min after administration, the sedative effect interfered with the anxiolytic effect, thus the results of the anxiolytic effect were not interpretable. From 30 min to 60 min after administration, this interference disappeared, the cerebral level of benzodiazepines was stable (the brain elimination of diazepam was compensated for by the appearance of desmethyldiazepam followed by oxazepam) but the anxiolytic effect decreased dramatically in all the tests with diazepam 1 mg/kg or 1.5 mg/kg. The acute tolerance to benzodiazepines and the difference of affinity for subtypes of GABA(A) receptors between diazepam, desmethyldiazepam, oxazepam could explain this result.

Objective—To evaluate the thermal antinociceptive effects and duration of action of buprenorphine hydrochloride after IM administration to American kestrels (Falco sparverius). Animals—12 healthy 3-year-old American kestrels. Procedures—Buprenorphine hydrochloride (0.1, 0.3, and 0.6 mg/kg) and a control treatment (saline [0.9% NaCl] solution) were administered IM in a randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus. Adverse effects were monitored for 6 hours after treatment administration. Results—Buprenorphine hydrochloride at 0.1, 0.3, and 0.6 mg/kg, IM, increased thermal threshold for 6 hours, compared with the response for the control treatment. There were no significant differences among buprenorphine treatments. A mild sedative effect was detected at a dose of 0.6 mg of buprenorphine/kg. Conclusion and Clinical Relevance—At the doses tested, buprenorphine hydrochloride resulted in thermal antinociception in American kestrels for at least 6 hours, which suggested that buprenorphine has analgesic effects in this species. Further studies with longer evaluation periods and additional forms of noxious stimuli, formulations, dosages, and routes of administration are needed to fully evaluate the analgesic effects of buprenorphine in American kestrels.

Small platform (SP) stress was induced by placing mice on small platforms (3.5 cm diameter) surrounded by water for 24 h. This model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. The staircase test consisted of placing a mouse in an enclosed staircase with 5 steps and recording (1) the number of steps and (2) rearings made during 3 min. SP stress increased the exploratory activity of mice in the staircase test as evidenced by an increase in the number of steps and rearings made In control mice diazepam (0.25 and 0.5 mg/kg) induced an anxiolytic effect in the staircase test as evidenced by a decrease in the number of rearings without changes in the number of steps. In SP stressed mice the anxiolytic effect of diazepam was not seen and the sedative effect as evidenced by a decrease in the number of steps was more pronounced. Buspirone at a dose of 1.0 mg/kg did not have effect on the behaviour of control or SP stressed mice in the staircase test. To study possible diurnal variations the staircase test was carried out at 3 different times of a day (08:00, 14:00, 20:00) with control and SP stressed mice. The exploratory activity of control mice in the staircase test gradually increased from 08:00 to 20:00 as evidenced by an increased number of steps and rearings made. SP stress increased the exploratory activity of mice irrespective of the time of testing. In conclusion, on the basis of these data the authors can propose that SP stress increases the exploratory activity of mice in the staircase test and induces a hyposensitivity of mice to the anxiolytic effect of diazepam. The effect of SP stress on the behaviour of mice in the staircase test is not caused by the disruptance of diurnal rhythms.