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- ItemAcesso aberto (Open Access)Avaliação dos métodos analíticos do cloridrato de petidina e da relação entre seus aspectos de qualidade e regulatórios(Universidade Federal de São Paulo, 2022-02-09) Carvalho, Débora Xavier de [UNIFESP]; Calixto, Leandro Augusto [UNIFESP]; http://lattes.cnpq.br/3551420764621660A petidina é um analgésico opioide, que possui estrutura química semelhante à da morfina. É administrado principalmente na forma de solução injetável, sob forma de cloridrato de petidina. Esse fármaco pode gerar um metabólito hepatotóxico, a normeperidina, o que contribui para que este não seja um fármaco de primeira escolha. Além disso, está também sujeito a sofrer degradação hidrolítica do seu grupo éster e formar um composto ainda mais nocivo, o MPTP (N-metil-4-fenil-1,2,3,6-tetrahidropiridina). Não há metodologia para o cloridrato de petidina na última edição da Farmacopeia Brasileira, ao contrário das Farmacopeias Americana (USP) e Britânica (BP). Sendo que apenas na BP está incluída análise para identificação e quantificação do MPTP. Na literatura, métodos por eletroforese capilar demostraram-se eficientes como técnicas complementares; e o método por HPLC-MS demonstrou ser ainda mais sensível que o método farmacopeico de referência. Considerando-se que, no Brasil, atualmente tem-se registrados 3 medicamentos com o princípio ativo cloridrato de petidina, e analisando aspectos regulatórios (como as notificações de eventos adversos), é notória a criticidade da utilização deste medicamento e a necessidade da inclusão e desenvolvimento de métodos analíticos complementares que ajudem a garantir a segurança do paciente durante a administração do fármaco.
- ItemSomente MetadadadosThe COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats(Elsevier B.V., 2007-04-10) Reksidler, Angela B.; Lima, Marcelo M. S.; Zanata, Silvio M.; Machado, Hidevaldo B.; Cunha, Claudio da; Andreatini, Roberto; Tufik, Sergio [UNIFESP]; Vital, Maria A. B. F.; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib (Bextra (TM)) in the prevention of motor and cognitive impairments observed in rats after an intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of the early phase of Parkinson's disease. the treatment with parecoxib (10 mg/kg) administered prior to the surgery and daily (2 mg/kg) for the subsequent 21 days, prevented the MPTP-treated rats from presenting decreased locomotor and exploratory behavior, increased immobility, and impairment while performing the cued version of the Morris water maze. Furthermore, parecoxib treatment also significantly prevented the reduction of tyrosine hydroxylase protein expression in the substantia nigra (7, 14 and 21 days after surgery), and in the striatum (14 and 21 days after surgery) as immunodetected by western blotting. These results strongly suggest that parecoxib exerts a neuroprotective effect on motor, tyrosine hydroxylase expression, and cognitive functions as it prevents their impairments within the confines of this animal model of the early phase of Parkinson's disease. (c) 2007 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosDistinct Effects of Intranigral L-DOPA Infusion in the MPTP Rat Model of Parkinson's Disease(Springer, 2009-01-01) Reksidler, Angela B.; Lima, Marcelo M. S.; Dombrowski, Patricia A.; Barnabe, Gabriela F. [UNIFESP]; Andersen, Monica L. [UNIFESP]; Tufik, Sergio [UNIFESP]; Vital, Maria A. B. F.; Universidade Federal de Santa Catarina (UFSC); Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)The potential neuroprotective or neurotoxic effects of 3,4-dihydroxyphenylalanine (L-DOPA) are yet to be understood. We examined the behavioral, immunohistochemical, tyrosine hydroxylase (TH) expression and neurochemical parameters after an intranigral administration of L-DOPA (10 mu M) in rats.. L-DOPA elicited a 30.5% reduction in dopaminergic neurons, while 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (100 mu g mu L(-1)) produced a 53.6% reduction. A combined infusion of MPTP and L-DOPA generated a 42% reduction of nigral neurons. Motor parameters revealed that both the MPTP and L-DOPA groups presented impairments; however, the concomitant administration evoked a partial restorative effect. in addition, MPTP and L-DOPA separately induced reductions of TH protein expression within the substantia nigra. in contrast, the coadministration of MPTP and L-DOPA did not demonstrate such difference. the striatal levels of dopamine were reduced after MPTP or L-DOPA, with an increased turnover only for the MPTP group. in view of such results, it seems reasonable to suggest that L-DOPA could potentially produce dopaminergic neurotoxicity.
- ItemSomente MetadadadosHemiparkinsonian rats rotate toward the side with the weaker dopaminergic neurotransmission(Elsevier B.V., 2008-06-03) Da Cunha, Claudio; Wietzikoski, Evellyn Claudia; Ferro, Marcelo Machado; Martinez, Glaucia Regina; Barbato Frazao Vital, Maria Aparecida; Hipolide, Debora [UNIFESP]; Tufik, Sergio [UNIFESP]; Canteras, Newton Sabino; Universidade Federal do Paraná (UFPR); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have been used as a model of Parkinson's disease. Depending on the lesion protocol and on the drug challenge, these rats rotate in opposite directions. the aim of the present study was to propose a model to explain how critical factors determine the direction of these turns. Unilateral lesion of the SNpc was induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Separate analysis showed that neither the type of neurotoxin nor the site of lesion along the nigrostriatal. pathway was able to predict the direction of the turns these rats made after they were challenged with apomorphine. However, the combination of these two factors determined the magnitude of the lesion estimated by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal dopamine. Very small lesions did Dot cause turns, medium-size lesions caused ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc lesions resulted in an increased binding of [H-3] raclopride to D2 receptors, while medium-size lesions reduced the binding of [H-3]SCH-23390 D1 receptors in the ipsilateral striatum. These results are coherent with the model proposing that after challenged with a dopamine receptor agonist, unilaterally SNpc-lesioned rats rotate toward the side with the weaker activation of dopamine receptors. This activation is weaker on the lesioned side in animals with small SNpc lesions due to the loss of dopamine, but stronger in animals with large lesions due to dopamine receptor supersensitivity. (C) 2008 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosIntra-nigral MPTP lesion in rats: Behavioral and autoradiography studies(Elsevier B.V., 2005-10-01) Perry, J. C.; Hipolide, D. C.; Tufik, S.; Martins, R. D.; Da Cunha, C.; Andreatini, R.; Vital, MABF; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)The present study investigated the motor response and possible changes in binding to D-1 and D-2 receptors after intra-nigral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. the results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. in addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [H-3]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [H-3]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D I dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats. (c) 2005 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosMelatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats(Elsevier B.V., 2008-10-10) Capitelli, Caroline; Sereniki, Adriana; Santos Lima, Marcelo Meira [UNIFESP]; Reksidler, Angela Braga; Tufik, Sergio [UNIFESP]; Barbato Frazao Vital, Maria Aparecida; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)Parkinson's disease is a chronic neurological disease characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. Melatonin is a powerful antioxidant agent secreted by the pineal gland which has numerous physiological functions and seems to exert an important neuroprotective effect. the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model has been used to understand the pathophysiology of the disease because of its capacity to mimic biochemical and histological features observed in Parkinson's disease. This study investigated the effect of pretreatment with melatonin (50 mg/kg) on MPTP-lesioned animals 24 h and 7 days after neurotoxin infusion using the open-field test, two-way avoidance task and immunohistochemistry. Twenty-four hours after lesioning, the MPTP+vehicle group exhibited hypolocomotion and significant loss of tyrosine hydroxylase-immunoreactive cells, whereas no differences in these parameters were observed in lesioned animals receiving melatonin. Seven days after surgery, the MPTP-lesioned rats did not show hypolocomotion compared to control animals, while there was a significant dopaminergic neuronal loss. in the two-way avoidance task, MPTP-treated animals presented a cognitive deficit compared to the control groups and melatonin administration did not repair this defect. the present results suggest that melatonin reduces neuronal loss in the MPTP animal model of Parkinson's disease. (C) 2008 Published by Elsevier B.V.
- ItemSomente MetadadadosRepeated intranigral MPTP administration: A new protocol of prolonged locomotor impairment mimicking Parkinson's disease(Elsevier B.V., 2008-01-30) Reksidler, Angela Braga; Lima, Marcelo Meira Santos [UNIFESP]; Dombrowski, Patricia; Andersen, Monica Levy [UNIFESP]; Zanata, Silvio Marques; Andreatini, Roberto; Tufik, Sergio [UNIFESP]; Vital, Maria Aparecida Barbato Frazao; Universidade Federal de São Paulo (UNIFESP); Univ Fed ParanaDifferent Parkinson's disease (PD) animal models reproduce the early phase of the disease, which deny the possible existence of a synergic effect of consecutive insults to the dopaminergic neurons. We proposed a novel protocol of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nigrostriatal lesion, which consists in repeated MPTP intranigral administrations intending to differentiate effects of a single lesion in relation to repeated lesions. for this purpose, a schedule of 3-day intervals between the MPTP administrations, totalizing 3 infusions in 9 days were adopted. A persistent locomotor deficit was produced after the 2nd infusion, remaining until the last time-point. Tyrosine hydroxylase (TH) immunoreactive neurons were reduced in 50% 1 day after the 1st infusion and the neuronal loss remained constant even after the 2nd and 3rd MPTP infusions. in parallel, (TH) protein expression in the substantia nigra pars compacta (SNpc) revealed to be a sensitive target for MPTP, once it was found to be down-regulated immediately after the 1st MPTP exposure until the last time-point. These findings corroborate the concept of an early phase model of PD elicited by MPTP even when this neurotoxin was used according to the protocol currently proposed. the current protocol provided relevant insights about TH expression and irreversible locomotor impairment. (c) 2007 Elsevier B.V. All rights reserved.