Navegando por Assunto "Antidepressivo"
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Item Acesso aberto (Open Access) Avaliação pré-clínica da duloxetina em modelo de convulsão: análise comportamental, eletroencefalográfica e influência no estresse oxidativo(Universidade Federal do Pará, 2014-06-17) COELHO, Danielle Santana; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265Epilepsy is a disorder with high prevalence and severity. Although there are several anticonvulsant drugs available in the market, 30 to 40% of the patients are refractory to the treatment. Besides the seriousness of epilepsy per se, this disorder may be accompanied by many comorbidities such as depression, which is the main psychiatric comorbidity of epilepsy. The mechanisms involved in the relationship between epilepsy and depression are not clarified. Given that some anticonvulsant drugs can trigger or enhance depressive symptoms, while some antidepressant drugs can potentiate the severity of seizure, the concomitant treatments of both disorders can be problematic. On the other hand, some studies have shown that antidepressant drugs can be safe and even possess an anticonvulsant activity such as venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI). Considering that duloxetine, another SNRI, has a more potent inhibition of monoaminergic transporters and that there is no study about its influence on seizures, the aim of our study is to verify the potential anticonvulsant action of duloxetine against seizures induced by pentylenetetrazole (PTZ) on mice. With this aim, mice will be pre-treated with duloxetine (10, 20, 40 mg/kg/i.p.), and thirty minutes after, the animals will receive an intraperitoneal injection of PTZ (60 mg/kg, i.p.). In the following twenty minutes the animals are going to be evaluated. The threshold for the first myoclonic jerk, tonic-clonic seizure, the duration of seizures and survival will be quantified. The electroencephalographic analysis (EEG) was used to assess the severity of the seizures (wave’s amplitude increase). After this period the animals will be sacrificed, the cerebral cortex dissected and biochemical analysis (activity of superoxide dismutase (SOD), catalase (CAT), nitrite levels and lipid peroxidation) will be made to investigate the mechanisms by which this drug can influence seizures. The results exhibit the anticonvulsant action of duloxetine. The drug was capable of enhancing the threshold for the first myoclonic and tonic-clonic seizures induced by PTZ. Additionally, the EEG demonstrated that duloxetine at the dose of 20 mg/kg decreased significantly the amplitude of the waves while at the dose of 40 mg/kg it increased the amplitude when compared to all the treatments. Regarding the evaluation of duloxetine’s influence on oxidative stress, all the animals treated solely with PTZ presented a significant increase on lipid peroxidation and a decrease on SOD and CAT activity. Concerning nitrites’ level, there was no difference between the treatments. The dose of 20 mg/kg of duloxetine showed a significant protection against the alterations in oxidative stress induced by PTZ. The anticonvulsant action of duloxetine (20 mg/kg) collaborates with the theory which has been presented in the last few years where it is proposed that the modulation of the serotonergic and noradrenergic neurotransmission may exert an anticonvulsant activity. Moreover, the efficiency of duloxetine in preventing the aggravation of oxidative stress involved in the seizures induced by PTZ corroborates with studies that demonstrate that anticonvulsant substances can influence seizures through its antioxidant activity. Given these points, we conclude that duloxetine is a promising adjuvant for the treatment of patients with the comorbidity epilepsy and depression.Item Acesso aberto (Open Access) Determinação das concentrações plasmáticas de amitriptilina por cromatografia líquida de alta eficiência em pacientes com hanseníase e estados reacionais(Universidade Federal do Pará, 2008-10-24) MORAES, Tânia Mara Pires; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Leprosy is a granulomatous disease affecting the skin and peripheral nerves caused by Mycobacterium leprae. The alterations in peripheral nerves can originate pain symptoms and deformities, with consequent reduction of patient life quality. Amitriptyline is the drug of choice for the treatment of pain symptoms in patients with leprosy. Amitriptyline had a narrow therapeutic range and a great variability in plasmatic concentrations between patients. Thus the therapeutic monitoring of the plasmatic concentrations of this drug its a important tool for therapy optimization. In this sense this work aimed the validation of an analytical procedure for determination of amitriptyline by high performance liquid chromatography, in patients with hansenic reactions using amitriptyline daily doses of 25mg or 50mg, as well make the comparison between amitriptyline plasmatic concentrations in the presence or absence of multidrug therapy and in the reactions type I and II. This study was conducted in Tropical Medicine Institute from Para Federal University. Were enrolled 21 patients, 12(57%) male and 9 (43%) female. Eight patients (38%) were in curse of multidrug therapy and 10 (47%) presented hansenic reaction type I. The medium plasmatic amitriptyline concentration in dose of 25mg was 318144ng/mL and 361182ng/mL. No statistical significance was observed between medium plasmatic amitriptyline concentrations in doses of 25mg and 50mg, as well in the presence of multidrug therapy.Item Acesso aberto (Open Access) Efeitos do tratamento subcrônico com fluoxetina sobre os comportamentos e parâmetros oxidativos de ratos submetidos ao exercício físico exaustivo(Universidade Federal do Pará, 2017-08-25) LEAL, Jerusa de Carvalho; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390Fluoxetine is an antidepressant drug of the selective serotonin reuptake inhibitor class, its use may be a therapeutic alternative in reversing or reducing the changes caused by low serotonergic activity. The increase in serotonergic levels can also be induced by regular physical exercise, in that sense, the health benefits and the prevention of diseases that this type of exercise are promoted are already well reported. However, when exercise is practiced exhaustively it may induce increased oxidative stress and changes in emotional behavior in humans and experimental animals. Therefore, the objective of this study was to evaluate the effects of subchronic treatment with fluoxetine on the behavior and oxidative parameters in rats submitted to exhaustive physical exercise in forced swimming. Therefore, adult male rats of Wistar strain were divided into sedentary animals and exposed to exhaustive exercise subcronically that were treated with fluoxetine 10 mg / kg / day (NaCl 0.9%) and saline either via i.p. for 7 days. After 30 minutes of intoxication the animals were individually exposed to exhaustive physical exercise for 20 minutes. On the eighth day of the experiment, the open field test (TCA) and the high cross labyrinth (LCE) were performed to evaluate spontaneous locomotion and anxiety - like behavior, respectively. The animals were then authanized and blood, liver and brain were collected for determination of GSH, TEAC, NO, and MDA levels. The results obtained, the animals treated with fluoxetine associated to exhaustive physical exercise showed reduction in the locomotion caused by the emotional stress in the ACT and reduction in the behavior similar to the anxiety in the LCE. Regarding the parameters of oxidative stress, fluoxetine associated with the practice of exhaustive physical exercise, in general, induced oxidative stress in the organism, mainly in the blood and liver of these animals, with reduction of the levels of GSH and TEAC and increase of levels of NO and MDA. On the other hand, in the brain, treatment with fluoxetine showed protective effect on oxidative stress, with reduction in NO and MDA levels and increase in antioxidant factors. On the data, it is concluded that fluoxetine associated with exhaustive exercise has dual effect of activity in relation to neurobehavioral and oxidative balance, reducing movement and increasing the anxiolytic effect, demonstrating antioxidant or pro-oxidant depending on the tissue or organ evaluated.