RESUMO

Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.

Assuntos

Ansiolíticos , Óleos Voláteis , Camundongos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Hipnóticos e Sedativos/farmacologia , Projetos de Pesquisa , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ansiedade/tratamento farmacológico , Diazepam/farmacologia , Óleos Voláteis/farmacologia , Aprendizagem em Labirinto , Flores , Comportamento Animal

RESUMO

A castração química é utilizada para castrar cães machos a um custo mais baixo que o procedimento cirúrgico, que é o método mais aplicado para castrar cães e gatos. A castração química é um procedimento mais simples que a castração cirúrgica e pode ser realizada a nível ambulatorial, sem necessidade de anestesia geral. Entretanto, devido ao estresse pela manipulação e ao desconforto produzido pela injeção de uma substância no interior dos testículos, faz-se necessária uma sedação para que a castração química seja efetuada de um modo que proporcione o bem-estar do animal. Assim, este artigo tem como objetivo propor um protocolo inovador para sedação de cães submetidos à castração química. Para isso, foram utilizados 12 cães submetidos à administração de xilazina em subdose no acuponto yin tang. Após o estabelecimento da sedação, os cães foram castrados quimicamente. O protocolo proposto permitiu que a castração química fosse realizada com conforto para o paciente e para a equipe de médicos veterinários. Desta forma, concluiu-se que o protocolo de sedação é seguro e pode ser empregado em cães para procedimentos não invasivos, como exames, coleta de material e outros processos ou técnicas semelhantes.

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Chemical castration is used to spay male dogs at a lower cost than the surgical procedure, which is the most applied method to spay dogs and cats. Chemical castration is a simpler procedure than surgical castration and can be performed on an outpatient basis, without the need for general anesthesia. However, due to the stress caused by manipulation and the discomfort produced by the injection of a substance into the testicles, sedation is necessary so that chemical castration is to be carried out in a way that provides the animal's welfare. Thus, this article aims to propose an innovative protocol for sedation of dogs submitted to chemical castration. For this purpose, twelve dogs submitted to the administration of xylazine in subdosis in the yin-tang acupoint were used. After the establishment of sedation, the dogs were chemically neutered. The proposed protocol allowed chemical castration to be performed with comfort for the patient and the team of veterinarians. Therefore, it is concluded that the sedation protocol is safe and can be used in dogs for non-invasive procedures such as exams, material collection, and other similar processes or techniques.

Assuntos

Animais , Masculino , Cães , Xilazina/administração & dosagem , Analgesia por Acupuntura/veterinária , Cefalotina/administração & dosagem , Acupuntura/métodos , Meloxicam/administração & dosagem , Orquiectomia/métodos , Orquiectomia/veterinária

RESUMO

Plectranthus neochilus Schltr. (Lamiaceae) is a plant recently introduced in Cuba. Worldwide, it is an ethnomedicinal alternative for its use against microbial infections, but the Cuban population use the extracts to treat sleep disorders. To address this apparent incongruity, four collections (from different seasonal conditions in the year) of Cuban P. neochilus cultivars were analyzed in terms of their pharmacognostic characteristics. Three extracts using fresh and dried leaves were chemically and biologically characterized. UPLC-DAD-MS/MS analysis was performed to determine their chemical composition, while a panel of nine microorganisms was used to evaluate their antimicrobial activity. Finally, cytotoxic effects of different fractions were measured in three cell lines by the resazurin viability assay. In contrast to previously reported micro and macromorphological properties of P. neochilus, the leaves from the Cuban cultivars did not present glandular trichomes, nor did they produce quantifiable levels of essential oils. Moreover, aqueous extracts used by the population revealed no significant antimicrobial activity and were not cytotoxic. The three extracts showed a similar phytochemical composition, i.e., eight flavonoids, seven abietane diterpenes, and rosmarinic acid as the major constituent, most of them reported for the first time in this species. The low yield of essential oil, the absence of glandular trichomes, compounds with a high level of oxidation, and a moderate antimicrobial activity detected were the most distinctive pharmacognostic and biological characteristics of P. neochilus grown in Cuba. These aspects could explain its non-use as an antimicrobial.

RESUMO

Background: The Brazilian tapir (Tapirus terrestris), considered the largest land mammal in South America, is a vulnerable species in terms of its degree of conservation. In captivity, its health is evaluated through behavioral and physical observation and laboratory exams, and in some cases, chemical restraint, to reduce stress. Dissociative anesthetics and sedatives are used for the sedation of these animals, and few studies have reported the use of dexmedetomidine and its effects when associated with other drugs in chemical containment protocols; therefore, this work reports its use, in conjunction with ketamine and midazolam, in a young Brazilian tapir. Case: A male Brazilian tapir, male, weighing 89 kg, 1 and a half year old, housed at CETAS in Rio Branco, Acre, was chemically restrained with dexmedetomidine (7 µg/kg), ketamine (1.5 mg/kg), and midazolam (0.2 mg/kg) for venous blood collection, oral and rectal mucosal swabs, and microchipping. The protocol was administered intramuscularly to the right triceps brachii, after physical restraint. After 5 min of application, the animal assumed sternal recumbency and presented reflux. After 15 min, the patient was placed in the right lateral decubitus position. During collection, heart rate (48 ± 10 bpm), respiratory frequency (29 ± 1 mpm), rectal temperature (38.1 ± 0.18°C), oxyhemoglobin saturation (97 ± 1%), and electrocardiographic tracing were recorded. The tapir showed deep sedation, immobility, good muscle relaxation, discreet medial palpebral reflex, and bilateral rotation of the eyeball. After 40 min of protocol administration, sedative reversal was performed intramuscularly with 14 µg/kg atipamezole. Five min after administration, the tapir showed signs of mild sedation. After 10 min, he assumed the quadrupedal position, remained in this position for 8 min, and gently resumed the sternal decubitus. After only 20 min, he resumed the quadrupedal position, with mild ataxia and good muscular and conscious tone. After 50 min, the patient was discharged from anesthesia. Discussion: Domestic horses are phylogenetically close to tapirs, so the choice of drugs and doses of the protocol used was based on their use in horses, and on studies carried out with tapirs as well. Despite being docile and passive, the tapir was not conditioned and did not allow the manipulation and collection of samples collaboratively; therefore, it was chemically contained. The physical restraint performed did not generate satisfactory immobilization of the tapir, resulting in agitation and stress and causing the needle to break. The reflux presented by the tapir minutes after sedation and at recovery was induced by dexmedetomidine, and only the undigested banana pieces were offered to the animal. Reflux plus stress from extensive fasting and suboptimal physical restraint was responsible for the change in the tapir's eating behavior, with possible stress gastritis 24 h after chemical restraint. Only one study reported the use of dexmedetomidine in tapirs, associated with continuous infusions of ketamine, midazolam and guaiacol glyceryl ether for moderate to long-term field procedures. Sedative reversal of dexmedetomidine by atipamezole reduced the recovery time and the risk of death from cardiorespiratory depression. The anesthetic combination used was effective, promoting immobility, muscle relaxation, and stability of the physical parameters evaluated, with rapid and gentle induction and an adequate level of sedation for the objective, good sedative reversal, and anesthetic recovery.

Assuntos

Animais , Masculino , Perissodáctilos/fisiologia , Dexmedetomidina/administração & dosagem , Dexmedetomidina/análise , Animais Selvagens/fisiologia

RESUMO

The biological and pharmacological properties of natural polyphenols of the extract of Euterpe oleracea stone (EEOS) are associated with the central nervous system (CNS). To investigate the sedative and myorelaxant activity of EEOS in vivo, this study aimed to present the myorelaxant and sedative effects of EEOS in Wistar rats using spontaneous locomotor activity and motor electrophysiology. A total of 108 animals were used in the following experiments: a) behavioral tests (n = 27); b) electromyographic recordings of skeletal muscle (n = 27); c) respiratory muscle activity recordings (n = 27); d) cardiac muscle activity recordings (n = 27). The behavioral characteristics were measured according to the latency time of onset, the transient loss of posture reflex and maximum muscle relaxation. Electrodes were implanted in the gastrocnemius muscle and in the tenth intercostal space for electromyographic (EMG) signal capture to record muscle contraction, and in the D2 lead for electrocardiogram acquisition. After using the 300 mg/kg dose of EEOS intraperitoneally, a myorelaxant activity exhibited a lower frequency of contractility with an amplitude pattern of low and short duration at gastrocnemius muscle and intercostal muscle, which clearly describes a myorelaxant activity and changes in cardiac activity. The present report is so far the first study to demonstrate the myorelaxant activity of this extract, indicating an alternative route for açai stone valorization and its application in pharmaceutical fields.

RESUMO

Ten male sheep (Sheep group; SGk) and seven male goats (Goat group; GGks+) were used in this study. The objective was to compare the use of racemic ketamine or ketamine S(+) associated with lidocaine on spinal anesthesia and evaluate if the drugs leads to a surgical anesthesia state, as well as to verify the cardiorespiratory, sedative and motor effects of this technique in these species. After correct placement of the needle in the subarachnoid space, 3.0 mg kg-1 of racemic ketamine (SGk) or ketamine S(+) (GGks+), both diluted in 1.5 mg kg-1 of 2% lidocaine, were administered. Evaluations were performed during orchiectomy, at times 0 (T0), 5 (T5), 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes after subarachnoid anesthesia administration. No significant changes in heart and respiratory rates were observed in both experimental groups. All animals showed surgical analgesia and stood conscious or slightly sedated with ataxia immediately after the drugs administration (T5), allowing the execution of bilateral orchiectomy. The ataxia in SGk was classified as severe with recumbency in 80% of the animals, moderate ataxia in 10% of the animals, and mild ataxia in 10% of the animals. All goats (GGks+; 100%) presented severe ataxia and recumbency. At 60 min, animals of both groups were in standing position and with normal gait. Subarachnoid RS-ketamine and ketamine S(+) (3 mg kg-1), associated with lidocaine in sheep and goats, produces surgical anesthesia and recumbency without causing cardiorespiratory abnormalities, regurgitation and bloating.

RESUMO

Aerial parts (leaves, flowers, stem) of Peperomia galioides extract administered to mice, was used to confirm its anti-inflammatory and sedative folk uses. The anti-inflammatory activity was assessed by croton oil-induced ear oedema and myeloperoxidase (acute inflammation); cotton pellet-induced granuloma (sub-acute inflammation) and Escherichia coli Lipopolysaccharide (LPS) induced inflammation (cellular mediators). The sedative activity was studied by the pentobarbital-induced sleeping time test. Single doses (300 and 600 mg/kg; i.p.) of the extract reduced croton oil-induced ear oedema and myeloperoxidase activity. Six days administration of the extract (300 mg/kg, i.p.) to mice implanted with cotton pellets diminished granuloma formation. LPS (20 mg/kg, i.p.) enhanced plasma nitrites and TNF-α levels that were inhibited by the extract. The duration but not the onset of sleeping time was enhanced by 300 and 600 mg/kg of the extract. Our results show that P. galioides has anti-inflammatory and sedative activities in mice, which validates its traditional use.

Assuntos

Anti-Inflamatórios não Esteroides/farmacologia , Hipnóticos e Sedativos/farmacologia , Peperomia/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Óleo de Cróton/toxicidade , Edema/induzido quimicamente , Edema/tratamento farmacológico , Hipnóticos e Sedativos/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Peroxidase/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Sono/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue

RESUMO

Oil in water nano-emulsions are drug delivery systems constituted by liquid lipophilic nano-droplets dispersed through the external aqueous phase, often reaching the kinetic stability with surfactant as stabilizers. Essential oils can be the oily phase or the source of bioactive compounds. In this study, the essential oil of Aeollanthus suaveolens-a plant used in folk medicine due to its psychopharmacological effects-was used for preparation of fine nano-emulsions by a low-energy titrating method. Monodisperse small nano-droplets (ca. 70 nm; PdI 0.200) were assembled by using blends of non-ionic surfactants, indicating modulation on surfactant system lead to altering the physical property. In a separate set of experiments, we investigated the role of this modulation on biological properties of the optimal nano-emulsion. The zebrafish embryos were more susceptible to the nano-emulsion than the bulk essential oil, showing the improved bioactivity due to nano-sizing. Therefore, adult zebrafish was treated, and paralysis was observed in the groups treated with the nano-emulsion, being this finding in accordance with hypnosis. At the same essential oil dose, another behavior was observed, suggesting that expected dose-dependent effects associated to sedative-hypnotics can be achieved by nano-sizing of psychoactive essential oils. This paper contributes to the state-of-art drug delivery systems by opening perspectives for novel sedative-hypnotics nano-emulsified essentials oils that can reach hypnotic effects at considerably lower dose, when compared with bulk materials, being useful for further completed dose-response studies.Graphical abstract.

Assuntos

Lamiaceae/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Emulsões , Nanotecnologia , Óleos Voláteis/química , Óleos de Plantas/química , Tensoativos , Água , Peixe-Zebra

RESUMO

Chamomile is one of the most ancient medicinal herbs known to mankind and among its traditional uses are the calming effects. However, few studies explored its effects on the central nervous system (CNS). In this study we further proceed with structural elucidation of polysaccharides from chamomile tea. A highly substituted 4-O-methyl-glucuronoxylan (fraction SN-50R) was purified and chemically characterized, presenting Xyl:GlcA ratio of 1.7:1, Mw of 500 kDa and total sugar content of 98%. Its bioactivity on pain and on CNS was explored. Animals treated with SN-50R presented antinociceptive effect and a dose-dependent decrease in the number of crossings in the activity chamber and in the open field test, as well as a significant reduction in the number of marbles buried when compared to control. These results suggest that SN-50R presented sedative and anxiolytic-like effects and may be contributing for the calming effects obtained by chamomile tea ingestion.

Assuntos

Analgésicos/farmacologia , Ansiolíticos/farmacologia , Camomila/química , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Chá/química , Xilanos/farmacologia , Animais , Feminino , Masculino , Camundongos , Plantas Medicinais/química , Polissacarídeos/farmacologia

RESUMO

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1-25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light-dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABAA receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1-10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.

Assuntos

Ansiolíticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Flavonas/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Teste de Desempenho do Rota-Rod , Convulsões/induzido quimicamente , Estricnina , Natação

RESUMO

Midazolam (MID) is a sedative drug which can be added in beverage samples as drug-facilitated-sexual assault (date rape drug). This type of drug has short half-life in biological fluids (not detectable) which often prevents the correlation between drug abuse and crime. In this work, we described a simple and low-cost method for fast screening and selective determination of MID in beverage samples (vodka, whiskey and red wine). For the first time, the electrochemical oxidation of MID was used for this purpose. The oxidation mechanism was studied using electrochemical techniques (cyclic and square-wave voltammetry) and computational simulations (density functional theory calculations). Differential-pulse voltammetry, boron-doped diamond electrode (BDDE), and Britton-Robinson (BR) buffer (pH = 2) were selected as electrochemical analysis technique, working electrode and supporting electrolyte, respectively. Different linear response ranges (4-25 µmol L-1 with r = 0.9972; 1-10 µmol L-1 with r = 0.9951; 1-15 µmol L-1 with r = 0.9982) and limits of detection (0.46, 0.43 and 0.33 µmol L-1) were obtained for the analysis of vodka, whisky, and red wine solutions, respectively. The precision and accuracy were satisfactory considering the low relative standard deviation values (RSD < 6.3%, n = 15) and minimal sample matrix effects (recovery values between 87 and 103%).

RESUMO

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

Assuntos

Animais , Masculino , Camundongos , Ansiedade/tratamento farmacológico , Ansiolíticos/uso terapêutico , Óleos Voláteis/uso terapêutico , Citrus/química , Moduladores GABAérgicos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Ansiolíticos/isolamento & purificação , Aprendizagem em Labirinto/efeitos dos fármacos , Hipnóticos e Sedativos/isolamento & purificação

RESUMO

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Assuntos

Sistema Nervoso Central/efeitos dos fármacos , Eucaliptol/farmacologia , Hyptis/química , Óleos Voláteis/farmacologia , Animais , Eucaliptol/toxicidade , Feminino , Hipercinese/tratamento farmacológico , Ketamina , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Óleos Voláteis/toxicidade , Folhas de Planta/química , Sono/efeitos dos fármacos

RESUMO

In feline veterinary practice sedation is often needed to perform diagnostic or minimally invasive procedures, minimize stress, and facilitate handling. The mortality rate of cats undergoing sedation is significantly higher than dogs, so it is fundamental that the sedatives provide good cardiovascular stability. Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist utilized in cats to provide sedation and analgesia, although studies have been utilized high doses, and markedly hemodynamic impairments were reported. The aim of this study was to prospectively investigate how the sedative and electrocardiographic effects of a low dose of DEX performing in cats. Eleven healthy cats were recruited; baseline sedative score, systolic arterial pressure, electrocardiography, and vasovagal tonus index (VVTI) were assessed, and repeated after ten minutes of DEX 5μg/kg intramuscularly (IM). A smooth sedation was noticed, and emesis and sialorrhea were common adverse effects, observed on average seven minutes after IM injection. Furthermore, electrocardiographic effects of a low dose of DEX mainly include decreases on heart rate, and increases on T-wave amplitude. The augmentation on VVTI and appearance of respiratory sinus arrhythmia, as well as sinus bradycardia in some cats, suggesting that DEX enhances parasympathetic tonus in healthy cats, and therefore will be best avoid in patients at risk for bradycardia.(AU)

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Na rotina clínica da medicina veterinária felina a sedação é frequentemente requerida para realização de procedimentos diagnósticos ou minimamente invasivos, para minimizar o estresse e facilitar o manuseio dos pacientes. A taxa de mortalidade de gatos submetidos à sedação é mais elevada do que em cães, por esse motivo, é fundamental que os sedativos confiram estabilidade hemodinâmica. A dexmedetomidina (DEX) é um α2-agonista utilizado em felinos para promover sedação e analgesia, porém os estudos têm utilizado doses elevadas, e com isso prejuízos hemodinâmicos importantes foram relatados. O objetivo desta investigação foi avaliar os efeitos sedativos e eletrocardiográficos da baixa dose de DEX em gatos. Para tal, onze felinos saudáveis foram recrutados, foram obtidos valores basais para escore de sedação, pressão arterial sistólica e eletrocardiografia, além do índice de tônus vaso vagal (ITVV). Após dez minutos da aplicação intramuscular (IM) de DEX 5μg/kg todos os exames foram repetidos. Após a DEX, sedação suave foi detectada, e a êmese e sialorreia foram efeitos adversos comuns, observados em média 7 minutos após a injeção IM. Ademais, os principais efeitos eletrocardiográficos foram redução na frequência cardíaca e aumento na amplitude da onda T. O ITVV mais elevado e surgimento de arritmia sinusal respiratória, bem como bradicardia sinusal em alguns gatos, sugerem que a DEX eleva o tônus parassimpático, e por esse motivo deve ser utilizada com cautela em pacientes com predisposição à bradicardia.(AU)

Assuntos

Animais , Gatos , Gatos , Dexmedetomidina , Sedação Profunda , Agonistas de Receptores Adrenérgicos alfa 2 , Bradicardia/veterinária

RESUMO

In feline veterinary practice sedation is often needed to perform diagnostic or minimally invasive procedures, minimize stress, and facilitate handling. The mortality rate of cats undergoing sedation is significantly higher than dogs, so it is fundamental that the sedatives provide good cardiovascular stability. Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist utilized in cats to provide sedation and analgesia, although studies have been utilized high doses, and markedly hemodynamic impairments were reported. The aim of this study was to prospectively investigate how the sedative and electrocardiographic effects of a low dose of DEX performing in cats. Eleven healthy cats were recruited; baseline sedative score, systolic arterial pressure, electrocardiography, and vasovagal tonus index (VVTI) were assessed, and repeated after ten minutes of DEX 5μg/kg intramuscularly (IM). A smooth sedation was noticed, and emesis and sialorrhea were common adverse effects, observed on average seven minutes after IM injection. Furthermore, electrocardiographic effects of a low dose of DEX mainly include decreases on heart rate, and increases on T-wave amplitude. The augmentation on VVTI and appearance of respiratory sinus arrhythmia, as well as sinus bradycardia in some cats, suggesting that DEX enhances parasympathetic tonus in healthy cats, and therefore will be best avoid in patients at risk for bradycardia.(AU)

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Na rotina clínica da medicina veterinária felina a sedação é frequentemente requerida para realização de procedimentos diagnósticos ou minimamente invasivos, para minimizar o estresse e facilitar o manuseio dos pacientes. A taxa de mortalidade de gatos submetidos à sedação é mais elevada do que em cães, por esse motivo, é fundamental que os sedativos confiram estabilidade hemodinâmica. A dexmedetomidina (DEX) é um α2-agonista utilizado em felinos para promover sedação e analgesia, porém os estudos têm utilizado doses elevadas, e com isso prejuízos hemodinâmicos importantes foram relatados. O objetivo desta investigação foi avaliar os efeitos sedativos e eletrocardiográficos da baixa dose de DEX em gatos. Para tal, onze felinos saudáveis foram recrutados, foram obtidos valores basais para escore de sedação, pressão arterial sistólica e eletrocardiografia, além do índice de tônus vaso vagal (ITVV). Após dez minutos da aplicação intramuscular (IM) de DEX 5μg/kg todos os exames foram repetidos. Após a DEX, sedação suave foi detectada, e a êmese e sialorreia foram efeitos adversos comuns, observados em média 7 minutos após a injeção IM. Ademais, os principais efeitos eletrocardiográficos foram redução na frequência cardíaca e aumento na amplitude da onda T. O ITVV mais elevado e surgimento de arritmia sinusal respiratória, bem como bradicardia sinusal em alguns gatos, sugerem que a DEX eleva o tônus parassimpático, e por esse motivo deve ser utilizada com cautela em pacientes com predisposição à bradicardia.(AU)

Assuntos

Animais , Gatos , Gatos , Dexmedetomidina , Sedação Profunda , Agonistas de Receptores Adrenérgicos alfa 2 , Bradicardia/veterinária

RESUMO

Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist with sedative and analgesic properties, with minimal respiratory effects. It is used as a sedative in the intensive care unit and the operating room. The opioid-sparing effect and the absence of respiratory effects make dexmedetomidine an attractive adjuvant drug for anesthesia in obese patients who are at an increased risk for postoperative respiratory complications. The pharmacodynamic effects on the cardiovascular system are known; however the mechanisms that induce cardioprotection are still under study. Regarding the pharmacokinetics properties, this drug is extensively metabolized in the liver by the uridine diphosphate glucuronosyltransferases. It has a relatively high hepatic extraction ratio, and therefore, its metabolism is dependent on liver blood flow. This review shows, from a basic clinical approach, the evidence supporting the use of dexmedetomidine in different settings, from its use in animal models of ischemia-reperfusion, and cardioprotective signaling pathways. In addition, pharmacokinetics and pharmacodynamics studies in obese subjects and the management of patients subjected to mechanical ventilation are described. Moreover, the clinical efficacy of delirium incidence in patients with indication of non-invasive ventilation is shown. Finally, the available evidence from DEX is described by a group of Chilean pharmacologists and clinicians who have worked for more than 10 years on DEX.

RESUMO

BACKGROUND: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. OBJECTIVE: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. METHOD: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). RESULTS: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. CONCLUSION: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

Assuntos

Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Hipnóticos e Sedativos/farmacologia , Ftalimidas/farmacologia , Animais , Ansiolíticos/síntese química , Ansiolíticos/química , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Humanos , Hipnóticos e Sedativos/síntese química , Hipnóticos e Sedativos/química , Ligantes , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Ftalimidas/síntese química , Ftalimidas/química , Receptores de Glutamato Metabotrópico/química , Receptores de N-Metil-D-Aspartato/química , Convulsões/tratamento farmacológico , Estereoisomerismo

RESUMO

Os fármacos agonistas alfa-2 adrenérgicos são empregados há décadas na rotina anestesiológica veterinária, e recentemente destacou-se no mercado a dexmedetomidina, que possui maior especificidade, seletividade e segurança em relação a fármacos como a xilazina, clonidina, romifidina e detomidina. O objetivo deste estudo foi revisar os efeitos, aplicações e vantagens do uso da dexmedetomidina com base na literatura. Este novo fármaco é de grande interesse ao anestesiologista por promover sedação, analgesia e relaxamento muscular mais potentes que outros sedativos, além de proporcionar outros efeitos benéficos, como a redução do consumo de oxigênio durante o período trans e pós-operatório e da quantidade de anestésicos gerais e analgésicos. Assim como os outros fármacos da classe dos agonistas alfa-2 adrenérgicos, a dexmedetomidina causa depressão do sistema cardiovascular de forma menos acentuada e, no sistema respiratório, ocorre discreta alteração na frequência respiratória e no volume/minuto. A dexmedetomidina pode ser utilizada associada a fármacos opioides e na anestesia dissociativa. Ainda possui a capacidade de ser revertida com fármacos antagonistas alfa-2 adrenérgicos, como o atipamezol.

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Alpha-2-adrenergic agonist drugs have been used for decades in the veterinary anesthesiology routine and recently dexmedetomidine has been well-regarded commercially due to its greater specificity, selectivity and safety compared to drugs such as xylazine, clonidine, romifidine and detomidine. The aim of this study was to review the effects, feasibility and advantages of using dexmedetomidine based on the literature. This new drug is of great interest to the anesthesiologist for providing sedation, analgesia and more potent muscle relaxation compared to other sedatives, in addition to providing other beneficial effects, such as a decrease in the trans- and postoperatively oxygen consumption and in anesthetics and analgesics dosages. Similar to other alpha-2 adrenergic agonists, dexmedetomidine causes cardiovascular depression, although less acute, as well as affecting the respiratory system by a slight change in respiratory rate and minute volume. Dexmedetomidine can be used in combination with opioid drugs and in dissociative anesthesia. It also has the ability to be reversed with alpha-2 adrenergic antagonist drugs, such as atipamezole.

Assuntos

Dexmedetomidina/análise , Dexmedetomidina/história , Dexmedetomidina/uso terapêutico , Medicina Veterinária , /análise , Anestesia/veterinária , Hipnóticos e Sedativos/análise

RESUMO

Os fármacos agonistas alfa-2 adrenérgicos são empregados há décadas na rotina anestesiológica veterinária, e recentemente destacou-se no mercado a dexmedetomidina, que possui maior especificidade, seletividade e segurança em relação a fármacos como a xilazina, clonidina, romifidina e detomidina. O objetivo deste estudo foi revisar os efeitos, aplicações e vantagens do uso da dexmedetomidina com base na literatura. Este novo fármaco é de grande interesse ao anestesiologista por promover sedação, analgesia e relaxamento muscular mais potentes que outros sedativos, além de proporcionar outros efeitos benéficos, como a redução do consumo de oxigênio durante o período trans e pós-operatório e da quantidade de anestésicos gerais e analgésicos. Assim como os outros fármacos da classe dos agonistas alfa-2 adrenérgicos, a dexmedetomidina causa depressão do sistema cardiovascular de forma menos acentuada e, no sistema respiratório, ocorre discreta alteração na frequência respiratória e no volume/minuto. A dexmedetomidina pode ser utilizada associada a fármacos opioides e na anestesia dissociativa. Ainda possui a capacidade de ser revertida com fármacos antagonistas alfa-2 adrenérgicos, como o atipamezol.(AU)

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Alpha-2-adrenergic agonist drugs have been used for decades in the veterinary anesthesiology routine and recently dexmedetomidine has been well-regarded commercially due to its greater specificity, selectivity and safety compared to drugs such as xylazine, clonidine, romifidine and detomidine. The aim of this study was to review the effects, feasibility and advantages of using dexmedetomidine based on the literature. This new drug is of great interest to the anesthesiologist for providing sedation, analgesia and more potent muscle relaxation compared to other sedatives, in addition to providing other beneficial effects, such as a decrease in the trans- and postoperatively oxygen consumption and in anesthetics and analgesics dosages. Similar to other alpha-2 adrenergic agonists, dexmedetomidine causes cardiovascular depression, although less acute, as well as affecting the respiratory system by a slight change in respiratory rate and minute volume. Dexmedetomidine can be used in combination with opioid drugs and in dissociative anesthesia. It also has the ability to be reversed with alpha-2 adrenergic antagonist drugs, such as atipamezole.(AU)

Assuntos

Medicina Veterinária , Dexmedetomidina/análise , Dexmedetomidina/história , Dexmedetomidina/uso terapêutico , Receptores Adrenérgicos alfa 2/análise , Anestesia/veterinária , Hipnóticos e Sedativos/análise

RESUMO

Annona muricata Linnaeus (Annonaceae), popularly known as graviola, is used in folk medicine as both sedative and anticonvulsant. This study correlates the neurochemical profile with the behavioral effects of the hydroalcoholic extract from the leaves of Annona muricata (HLEAM) in mice, proposing to elucidate their mechanism of action on the central nervous system. Flavonoids and phenolic compounds were identified and quantified by High Performance Liquid Chromatography (HPLC) method. The acute toxicity (median lethal dose - LD50) was determined by probitos method using the percentage of mortality based on the Hippocratic screen. HLEAM (25, 50 and 100 mg/kg) was tested, intraperitoneally (i.p.), in models of sedation, anxiety, motor coordination, and seizures. The endogenous levels of dopamine, norepinephrine and DOPAC were assayed by reverse-phase HPLC with electrochemical detection. The HPLC analysis of the extract revealed the presence of flavonoids (quercetin, isoquercitrin, quercitrin, rutin, and kaempferol) and phenolics acids (gallic, chlorogenic, ellagic and caffeic acids). The LD50 was 1091.7 mg/kg and Hippocratic screening indicated central nervous system depressant effect. HLEAM presented sedative effects at doses of 25, 50, and 100 mg/kg, as well as anxiolytic and anticonvulsant effects at a dose of 100 mg/kg. In addition, these effects were partially reversed by flumazenil. The monoamines analysis by HPLC showed that HLEAM decreased the level of norepinefrine and dopamine in the mouse brain striatum. Thus, the results indicate a possible interaction of HLEAM with the GABAergic and monoaminergic systems, adding medicinal value to the popular use of the plant for the treatment of behavioral and neurological disorders.