ABSTRACT
Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.
Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.
Subject(s)
Animals , Male , Mice , Parkinson Disease, Secondary/drug therapy , Monoamine Oxidase Inhibitors/therapeutic use , Antiparkinson Agents/therapeutic use , Parkinson Disease, Secondary/chemically induced , Reserpine/administration & dosage , Carbidopa/administration & dosage , Catalepsy/chemically induced , Levodopa/administration & dosage , Coumarins , Disease Models, Animal , Drug Combinations , Drug Evaluation, Preclinical , Haloperidol , Locomotion/drug effects , Mice, Inbred ICR , Monoamine Oxidase Inhibitors/administration & dosage , Antiparkinson Agents/administration & dosageABSTRACT
Objective To report the clinical and neuroimaging findings in a case series of vascular parkinsonism (VP). Methods Seventeen patients with VP were evaluated with motor, cognitive, and neuroimaging standardized tests and scales. Results All patients had arterial hypertension. Ten patients were male and the mean age of the whole sample was 75.8±10.1 years. The mean age of parkinsonism onset was 72.2±10.0 years. Common clinical features were urinary incontinence (88.2%), lower limb parkinsonism with freezing of gait and falls (82.3%), and pyramidal signs (76.4%). The mean Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr scores were 72.5±21.6 points and 3.3±0.9 points, respectively. Sixteen (94.1%) patients had freezing of gait and executive dysfunction. Twelve (70.5%) patients had probable vascular dementia. The mean dose of levodopa was 530.9 mg/day. Unresponsiveness to the drug was confirmed by a 6.9 mean point reduction in the UPDRS score after the “practically defined off” test. Conclusion This series provides a profile of VP with predominant lower-limb involvement, freezing of gait and falls, pyramidal signs, executive dysfunction, concomitant vascular dementia, and poor levodopa response. .
Objetivo Relatar os achados clínicos e de neuroimagem em parkinsonismo vascular (PV). Métodos Foram avaliados 17 pacientes com PV do ponto de vista motor, cognitivo e de neuroimagem através de testes e escalas padronizados. Resultados Dos 17 pacientes, 10 (58,5%) eram homens; a média de idade média foi 75,8±10,1 anos. Todos os pacientes eram hipertensos; a média de idade do início do parkinsonismo foi 72,2±10,0 anos. Achados clínicos mais frequentes: incontinência urinária (88,2%); parkinsonismo de membros inferiores com bloqueio de marcha e quedas (82,3%); sinais piramidais (76,4%). A média dos escores UPDRS e Hoehn-Yahr foram, respectivamente, 72,5±21,6 e 3,3±0,9 pontos. Dezesseis pacientes (94,1%) apresentaram bloqueio de marcha e disfunção executiva. Doze pacientes (70,5%) preencheram critérios para demência vascular provável. A dose média de levodopa foi 530,9 mg/dia e os pacientes tiveram uma baixa resposta à droga, tendo havido redução de apenas 6,9 pontos em média no escore UPDRS após o teste “practically-defined off”. Conclusão O perfil de PV encontrado neste estudo foi caracterizado por: envolvimento predominante de membros inferiores, com bloqueio de marcha e quedas; sinais piramidais; disfunção executiva; demência vascular concomitante e resposta pobre à levodopa. .
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Cerebrovascular Disorders/physiopathology , Parkinson Disease, Secondary/physiopathology , Activities of Daily Living , Antiparkinson Agents/therapeutic use , Cross-Sectional Studies , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/drug therapy , Cognition Disorders/physiopathology , Hypertension/complications , Levodopa/therapeutic use , Parkinson Disease, Secondary/drug therapy , Parkinson Disease, Secondary/etiology , Risk Factors , Surveys and Questionnaires , Treatment OutcomeABSTRACT
INTRODUCTION: Neuroimaging studies of elderly individuals reveal alterations in the white matter that are incompatible with the patientÆs parkinsonism, mistakenly classified as vascular parkinsonism (VP). METHOD: This study was conducted on a population composed of 20 patients with ParkinsonÆs disease (PD) whose neuroimaging exams revealed vascular alterations in the white matter and seven patients with VP in order to compare diagnostic criteria. RESULTS: Age at disease onset of patients with PD was 55±12 years and patients with VP it was 62±13 years. Twelve patients with PD and five patients with VP presented arterial hypertension; three patients with VP and two patients with PD presented gait impairment; all patients with VP presented rigidity and bradykinesia, six of them presented resting tremor; 19 patients with PD presented tremor and 19 of them presented rigidity, while 17 presented bradykinesia. When the symptoms and evolution of both diseases were compared, the vascular alterations in the white matter were considered unspecific. CONCLUSION: Since clinical symptoms are unspecific, a differential diagnosis requires neuroimaging, good response to levodopa and clinical evolution.
INTRODUÇÃO: Estudos de neuroimagem em idosos mostram alterações na substância branca que são incompatíveis com o parkinsonismo do paciente, erroneamente classificado como parkinsonismo vascular (PV). MÉTODO: Este estudo foi conduzido a partir de uma população de 20 pacientes com doença de Parkinson (DP) cujos exames de neuroimagem revelaram alterações vasculares na substância branca e sete pacientes com PV para comparar os critérios diagnósticos. RESULTADOS: A idade de início da doença dos pacientes com DP foi 55±12 anos e pacientes com PV foi 62±13 anos. Doze pacientes com DP e cinco pacientes com PV apresentaram hipertensão arterial; três pacientes com PV e dois pacientes com DP apresentaram alteração da marcha; todos os pacientes com PV apresentaram rigidez e bradicinesia, seis deles apresentaram tremor de repouso; 19 pacientes com DP apresentaram tremor e 19 deles apresentaram rigidez, enquanto 17 apresentaram bradicinesia. Quando os sintomas e a evolução de ambas as doenças foram comparadas, as alterações vasculares na substância branca foram consideradas inespecíficas. CONCLUSÃO: Como os sintomas clínicos são inespecíficos, um diagnóstico diferencial requer neuroimagem, boa resposta a levodopa e evolução clínica da doença.
Subject(s)
Humans , Male , Female , Aged , Brain/blood supply , Brain/pathology , Parkinson Disease, Secondary/diagnosis , Antiparkinson Agents/therapeutic use , Diagnosis, Differential , Levodopa/therapeutic use , Magnetic Resonance Imaging , Parkinson Disease, Secondary/drug therapyABSTRACT
A rare case of a 40-year-old lady with a sporadic variety of the pallido-pyramidal syndrome (PPS) is reported. She had marked parkinsonian features on the left side. Her single photon emission computed tomography showed left frontoparietal and basal ganglia hypoperfusion. CT scan and central motor conduction time were normal. She responded partially to a combination of trihexyphenydil and L dopa/C dopa therapy. In view of the diversity in the genetic, clinical and laboratory features, it is possible that PPS may be a heterogeneous condition.
Subject(s)
Adult , Antiparkinson Agents/administration & dosage , Female , Humans , Levodopa/administration & dosage , Parkinson Disease, Secondary/drug therapy , SyndromeABSTRACT
To study the effects of 6-hydroxydopamine (6-OHDA) and reduced glutathione (GSH) on the nigral dopaminergic neurons in brain slices in vitro, immolunohistochemical technique was used to observe the changes of TH-stained neurons, including cell bodies and the dendrites, in the substantia nigra (SN) of midbrain slices of rats after incubation for 1 h in the presence of GSH 15 min before and during the period of incubation with 6-OHDA. The results showed that cell bodies remained intact but dendrites were fragmented and truncated after treatment with 6-OHDA. The antioxidant GSH alone did not significantly affect the dendrites of SN neurons but prevented 6-O-HDA-induced damage of dendrites. It was concluded that glutathione may prevent 6-OHDA-induced dopaminergic neurodegeneration and play a protective role in dopaminergic neurons.
Subject(s)
Glutathione/therapeutic use , Neurons/pathology , Oxidopamine , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/drug therapy , Random Allocation , Rats, Sprague-Dawley , Substantia Nigra/pathology , Tyrosine 3-Monooxygenase/metabolismABSTRACT
Apresentamos breve revisão da literatura sobre os agonistas dopaminérgicos. Referimos os cinco receptores conhecidos e onde estão localizados, as vantagens e as desvantagens de sua utilização nos pacientes com a doença de Parkinson. Introduzidos com o objetivo principal de controlar as limitações da levodopa, aumentando a janela terapêutica, analisamos a farmacocinética, a eficácia e os efeitos colateria da cabergolina, do ropinirole e do pramipexole.
Subject(s)
Humans , Antiparkinson Agents/therapeutic use , Dopamine Agonists/therapeutic use , Levodopa/therapeutic use , Parkinson Disease, Secondary/drug therapy , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacokinetics , Dopamine Agonists/adverse effects , Dopamine Agonists/pharmacokinetics , Dopamine Antagonists/therapeutic useABSTRACT
Os autores registram o caso de uma paciente com parkinsonismo induzido pela flunarizina. Ressaltam um aspecto importante, relacionado ao tremor, que assumia características wilsonianas quando realizava a prova índice-nariz. A depressäo foi sintoma importante. A cura se efetivou pela retirada da droga e pelo uso de levedopa e de tremaril por período de três meses
Subject(s)
Humans , Female , Middle Aged , Parkinson Disease, Secondary/chemically induced , Flunarizine/adverse effects , Biperiden/therapeutic use , Parkinson Disease, Secondary/drug therapy , Levodopa/therapeutic useABSTRACT
Parkinsonismo consequente a intoxicaçöes exógenas tem sido relatado desde o início do século. Os agentes mais comumente implicados säo o manganês, o monóxido de carbono e o sulfureto de carbono. No presente relato descreve-se síndrome parkinsoniana consequente a exposiçäo aguda ao óxido de etileno. Manifestaçöes neurológicas como neuropatia periférica e distúrbios cognitivos relacionados à exposiçäo a este gás foram previamente descritas, porém näo foi encontrada na literatura registro de parkinsonismo consequente a esse tipo de intoxicaçäo exógena
Subject(s)
Humans , Male , Adult , Parkinson Disease, Secondary , Ethylene Oxide/poisoning , Parkinson Disease, Secondary/drug therapyABSTRACT
O parkinsonismo é uma das principais afecçöes neurológicas presentes em idosos. Säo abordados inicialmente aspectos referentes a caracterizaçäo clínica da síndrome parkinsoniana e sua diferenciaçäo em relaçäo a outras condiçöes neurológicas. A seguir säo expostas as possíveis etiologias que podem determinar o aparecimento do parkinsonismo. Finalizando säo considerados tópicos referentes ao tratamento das diversas formas de parkinsonismo
Subject(s)
Humans , Parkinson Disease, Secondary/drug therapy , Amantadine/therapeutic use , Diagnosis, Differential , Levodopa/therapeutic useABSTRACT
Para tratar de correlacionar la influencia de los trastornos cerebrovasculares en el desarrollo de cuadros parkinsonianos, 115 pacientes con ataques isquémicos transitorios cuyas edades oscilan entre 32 y 84 años fueron evaluados durante un año. Los pacientes recibieron tratamiento con antiagregantes plaquetarios. En ningún caso fueron tratados con neurolépticos, antagonistas del calcio y otras drogas que pudieran causar parkinsonismo. Durante el estudio, 8 pacientes desarrollaron un cuadro parkinsoniano que fue bilateral en 7 de ellos. El único caso asimétrico fue también el único que respondió al tratamiento con L dopa. Al comparar la incidencia registrada con la esperada observamos un valor significativamente mayor en nuestra serie. Estos hallazgos sugieren que los trastornos cerebrovasculares son factores que contribuyen en el desarrollo del parkinsonismo en el anciano