RESUMO
Parkinson's disease (PD) is a multisystem disorder that affects 2-3% of the population ≥ 65 years of age. The main pharmacologic agent use in the treatment of clinical symptoms of PD is levodopa (L-DOPA). However, the chronic use of L-DOPA might result in the emergence of motor complications such as motor fluctuation and dyskinesia. Previous studies have shown that the inter-individual variability and pharmacogenetic profile of PD patients seem to influence the occurrence of motor complications. For these reasons, the purpose of this study was to evaluate a possible relationship between DRD1 A48G and DRD3 Ser9Gly genetic variants with the occurrence of motor complications in PD patients in a Brazilian population. A total of 228 patients with idiopathic PD were enrolled. Patients were genotyped for DRD1 A48G and DRD3 Ser9Gly polymorphisms using PCR-RFLP. The univariate and multivariate analyses were performed to assess the association of these polymorphisms with the occurrence of motor fluctuation and dyskinesia in PD patients. Multiple Poisson regression analyses showed a protector effect to the occurrence of dyskinesia for individuals carrying of the DRD1 G/G genotype (PR 0.294; CI 0.09-0.87; p ≤ 0.020) after the threshold Bonferroni's. Besides, we verified risk increased to the occurrence of motor complications with daily L-DOPA dosage, disease duration, and users of rasagiline, selegiline, or entacapone (p < 0.05 for all). Our results suggest that the DRD1 A48G polymorphism and the presence of extrinsic and intrinsic factors may role an effect in the occurrence of dyskinesia in PD patients.
Assuntos
Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Receptores de Dopamina D3/genética , Antiparkinsonianos/farmacologia , Antiparkinsonianos/uso terapêutico , Catecóis/farmacologia , Catecóis/uso terapêutico , Estudos Transversais , Dopamina/fisiologia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Genótipo , Humanos , Indanos/farmacologia , Indanos/uso terapêutico , Levodopa/farmacologia , Levodopa/uso terapêutico , Atividade Motora , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Selegilina/farmacologia , Selegilina/uso terapêuticoRESUMO
In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.
Assuntos
Antidepressivos/farmacologia , Ilex paraguariensis/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Comportamento Exploratório/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Selegilina/farmacologia , NataçãoRESUMO
Preclinical studies indicate that selegiline (deprenyl), frequently used in some neurodegenerative diseases, exert protective effects on central nervous system neurons of individuals exposed to social isolation (SI). Furthermore, it has been suggested that SI produces neuronal dysfunction due in part to an excessive intracellular Ca(2+) overload. Since the main intracellular Ca(2+) buffering mechanism involves changes in the calcium-binding protein calbindin-D28k (CB), and that CB neuronal expression can increase in response to Ca(2+) transients, we hypothesized that chronic selegiline administration in early socially isolated animals could minimize cell CB expression as an indirect indicator of protective mechanism against Ca(2+) overload. In the present study male rats were weaned at postnatal day 21 (P21) and randomly assigned to social deprivation (SI) or control (SC) environments for 30 days (P21-51). SI animals were further subdivided in two experimental groups: socially deprived-saline (SI-SAL) and socially isolated-selegiline (SI-SEL) for additional 30 days (P52-82). Medial frontal CB immunoreactivity (CB-ir) neurons were quantitatively and qualitatively analyzed. The results obtained indicate that neocortical cells of adult rats submitted to early SI show a significant increase in the number of CB-ir neurons per cortical field, while selegiline treatment significantly reduces this parameter.
Assuntos
Cálcio/metabolismo , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Selegilina/farmacologia , Isolamento Social , Desmame , Animais , Calbindina 1 , Calbindinas , Córtex Cerebral/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
In this study we assessed the involvement of monoamine oxidase B (MAO-B), a key enzyme implicated in monoamine metabolism, on postoperative (plantar incision) and neuropathic (partial sciatic nerve ligation) pain models in mice. Paw incision submitted mice showed a significant decrease in mechanical threshold compared with the sham-operated mice, characterizing the development of mechanical allodynia. The selective and irreversible MAO-B inhibitor selegiline, at a dose sufficient to selectively inhibit MAO-B activity (10 mg/kg), showed an anti-allodynic effect from 0.5 to 6 h after incision. Likewise, partial sciatic nerve ligation submitted mice also developed mechanical allodynia, which was reversed by selegiline (10 mg/kg) from 2 to 6 h after treatment. In addition, a significant increase on striatal MAO-B activity was observed in neuropathic mice compared with the sham-operated animals, which was reversed by selegiline treatment. Taken together, our results showed that MAO-B seems to exert a critical role in the development of postoperative and neuropathic pain.
Assuntos
Monoaminoxidase/metabolismo , Neuralgia/enzimologia , Complicações Pós-Operatórias/enzimologia , Animais , Clorgilina/farmacologia , Clorgilina/uso terapêutico , Modelos Animais de Doenças , Feminino , Camundongos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Neuralgia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Teste de Desempenho do Rota-Rod , Selegilina/farmacologia , Selegilina/uso terapêuticoRESUMO
Unilateral microinjection of manganese into the rat substantia nigra pars compacta (SNpc) leads to the death of nigral neurons and a decrease in dopamine (DA) within the ipsilateral striatum. L-deprenyl, an irreversible inhibitor of monoamine oxidase B, appears to protect or rescue dopaminergic nigral neurons from the toxic effects of 6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropiridine (MPTP). In this study we aimed to investigate whether L-deprenyl is able to influence the manganese neurotoxic time course. L-deprenyl rescue activity was evaluated in discontinuous posology and its protective effect was evaluated in a continuous one. Apomorphine-induced rotational behavior and striatal tyrosine hydroxylase immunostaining (TH-IS) were evaluated in both conditions at 24 h, 72 h and 168 h after intranigral microinjections. Our results indicate a failure in L-deprenyl to influence the establishment and time course of rotational response to apomorphine. Strikingly, a further decrease in the tyrosine hydroxylase immunostaining, at 168 h post microinjection in L-deprenyl-treated rats was obtained. Our data revealed no correlation between an increasing rotational behavior and reduction in TH-IS.
Assuntos
Corpo Estriado/efeitos dos fármacos , Manganês/toxicidade , Fármacos Neuroprotetores/farmacologia , Selegilina/farmacologia , Substância Negra/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Corpo Estriado/metabolismo , Agonistas de Dopamina/farmacologia , Imuno-Histoquímica , Masculino , Inibidores da Monoaminoxidase/farmacologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Fotomicrografia , Ratos , Rotação , Substância Negra/metabolismo , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Increased levels of iron in specific brain regions have been reported in neurodegenerative disorders. It has been postulated that iron exerts its deleterious effects on the nervous system by inducing oxidative damage. In a previous study, we have shown that iron administered during a particular period of the neonatal life induces oxidative damage in brain regions in adult rats. The aim of the present study was to evaluate the possible protective effect of selegiline, a monoamino-oxidase B (MAO-B) inhibitor used in pharmacotherapy of Parkinson's disease, against iron-induced oxidative stress in the brain. Results have shown that selegiline (1.0 and 10.0 mg/kg), when administered early in life was able to protect the substantia nigra as well as the hippocampus against iron-induced oxidative stress, without affecting striatum. When selegiline (10.0 mg/kg) was administered in the adult life to iron-treated rats, oxidative stress was reduced only in the substantia nigra.
Assuntos
Animais Recém-Nascidos/fisiologia , Antioxidantes , Antiparkinsonianos/farmacologia , Química Encefálica/efeitos dos fármacos , Ferro/toxicidade , Inibidores da Monoaminoxidase/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Selegilina/farmacologia , Animais , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Gravidez , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Deprenyl is a selective monoamine oxidase (MAO) B inhibitor, widely used for treatment of Parkinson's disease. The present study shows that deprenyl treatment was able to improve mitochondrial function. Fourteen month old mice were injected i.p. with deprenyl (20 mg/kg) and killed 1.5 h after the administration. Different brain subcellular fractions were isolated from control and deprenyl-treated animals to evaluate the effect of deprenyl on nitric oxide synthase (NOS) activity. Oxygen consumption, hydrogen peroxide (H(2)O(2)) production, mitochondrial membrane potential and calcium-induced permeability transition (MPT) were studied in intact mitochondria. In addition, the effect of deprenyl on respiratory complexes and MAO activities were evaluated in submitochondrial particles (SMP). Monoamine oxidase activity was found to be decreased by 55% in mitochondria from deprenyl-treated animals and as a consequence, H(2)O(2) production was significantly decreased. Deprenyl inhibited NOS activity in cytosolic fractions and SMP by 40% and 55%, respectively. In similar conditions, SMP from deprenyl-treated animals showed increased cytochrome oxidase activity. A 51% increase in the oxygen uptake in state 3 (active respiration state) was found after deprenyl treatment, but no significant changes were observed in state 4 (resting respiration state). Deprenyl treatment protected against calcium-induced depolarization and was able to inhibit calcium-induced MPT. This work provides evidence that deprenyl treatment exerts an improvement of brain mitochondrial function, through a reduction of free radical production, prevention of calcium-induced MPT and maintaining a mitochondrial transmembrane potential.
Assuntos
Encéfalo/ultraestrutura , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Inibidores da Monoaminoxidase/farmacologia , Selegilina/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Beclometasona , Western Blotting , Cálcio/farmacologia , Interações Medicamentosas , Peróxido de Hidrogênio/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Modelos Biológicos , Monoaminoxidase/metabolismo , Óxido Nítrico Sintase/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo , Partículas Submitocôndricas/efeitos dos fármacosRESUMO
It has been demonstrated that postweaning social isolation alters dendritic development in the medial prefrontal cortex (mPFC) of the rat. In addition, (-)-deprenyl, a monoamine oxidase B (MAO-B) inhibitor, promotes dendritic growth in prefrontocortical pyramidal cells. This study examined whether prefrontocortical dendritic developmental impairment induced by postweaning social isolation is attenuated by chronic (-)-deprenyl administration. Weanling Sprague-Dawley male rats were randomly reared in social and isolated environments between postnatal days 21 and 51 (P21-P51). At P52, half of the animals were behaviorally evaluated in the open-field test and sacrificed for histological analysis. The remaining isolated rats were subdivided into saline- and daily (-)-deprenyl-treated animals for 30 additional days (P52-P82). Socially-reared rats remained undisturbed except for daily saline administration. At P82, all animals were behaviorally evaluated and sacrificed for histological analysis. Dendritic quantification of the Golgi-Cox-Sholl-stained neurons indicated that chronic (-)-deprenyl administration partially compensated the dendritic growth impairment induced by social isolation. In addition, both isolated-saline- and (-)-deprenyl-treated rats showed a sustained locomotor hyperactivity in the open-field test.
Assuntos
Dendritos/efeitos dos fármacos , Inibidores da Monoaminoxidase/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Selegilina/farmacologia , Isolamento Social , Animais , Forma Celular/efeitos dos fármacos , Dendritos/fisiologia , Comportamento Exploratório/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Células Piramidais/fisiologia , Células Piramidais/ultraestrutura , RatosRESUMO
The present study shows that deprenyl, a known inhibitor of monoamine oxidase B (MAO B), may generate changes in mitochondrial function. Brain submitochondrial membranes (SMP), synaptosomes and cytosolic fractions were incubated with different deprenyl concentrations and nitric oxide synthase (NOS) activity was measured. The effect of deprenyl on oxygen consumption, calcium-induced permeability transition and hydrogen peroxide (H(2)O(2)) production rates was studied in intact mitochondria. Respiratory complexes and monoamine oxidase activities were also measured in submitochondrial membranes. Incubation of brain submitochondrial membranes with deprenyl 10, 25 and 50 microM inhibited nitric oxide synthase activity in a concentration-dependent manner. The same effect was observed in cytosolic fractions and synaptosomes. Monoamine oxidase activity was inhibited at lower deprenyl concentrations (from 0.5 microM). Cytochrome oxidase (complex IV) activity was found 42% increased in the presence of 25 microM deprenyl in a condition of maximal nitric oxide synthase activity. Incubation of brain mitochondria with deprenyl 25 microM produced a 60% increase in oxygen uptake in state 3, but no significant changes were observed in state 4. Pre-incubation of brain mitochondria with deprenyl 0.5 and 1 microM inhibited calcium-induced mitochondrial permeability transition and decreased hydrogen peroxide production rates. Our results suggest that in vitro effects of deprenyl on mitochondrial function can occur through two different mechanisms, involving nitric oxide synthase inhibition and decreased hydrogen peroxide production.
Assuntos
Encéfalo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Inibidores da Monoaminoxidase/farmacologia , Selegilina/farmacologia , Animais , Western Blotting , Encéfalo/enzimologia , Encéfalo/fisiologia , Permeabilidade da Membrana Celular , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Peróxido de Hidrogênio/farmacologia , Camundongos , Mitocôndrias/enzimologia , Mitocôndrias/fisiologia , Óxido Nítrico Sintase Tipo I/metabolismoRESUMO
In this work, we report an alternative assay for the determination of the inhibitory effect on monoamine oxidase B (MAO-B) activity of probe compounds. Enzyme MAO-B exhibits fluorescence emissions when it is excited at 412 nm. Using an inexpensive blue LED-like excitation source, we measured the quenching of fluorescence intensity of MAO-B enzyme during the reaction with inhibitors. The applicability of the procedure is demonstrated by assays with l-deprenyl and berberine as inhibitors through the use of fluorescence studies. The IC(50) values of l-deprenyl and berberine were 0.04 and 90 microM, respectively. The K(I) values were 0.020 and 47 microM for l-deprenyl and berberine, respectively. These IC(50) and K(I) values were similar to the values obtained with a standard method. These results demonstrate the feasibility of this method as an alternative to follow the inhibitory effect on MAO-B.
Assuntos
Monoaminoxidase/metabolismo , Espectrometria de Fluorescência/métodos , Animais , Benzilaminas/química , Berberina/química , Berberina/farmacologia , Relação Dose-Resposta a Droga , Cinética , Luz , Camundongos , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Inibidores da Monoaminoxidase/metabolismo , Selegilina/química , Selegilina/farmacologiaRESUMO
Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 microM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells and the levels did not change as a result of treatment. Alpha-tocopherol (10-100 microM) and ascorbic acid (100 microM) did not attenuate the effects of dopamine. Selegiline (10 microM) produced significant increase (P < 0.01) in the induction of HO-1 by dopamine (more than six times the control values). The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.
Assuntos
Cardiotônicos/farmacologia , Dopamina/farmacologia , Heme Oxigenase (Desciclizante)/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Selegilina/farmacologia , Northern Blotting , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1 , Humanos , Proteínas de Membrana , Neuroblastoma/patologia , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
La enfermedad de Parkinson requiere la administración de diversos fármacos. En el siguiente artículo se describen las diferentes drogas utilizadas, -agentes dopaminérgicos, anticolinérgicos y neuroprotectores- sus modos de acción, efectos adversos y precauciones y advertencias (AU)
Assuntos
Humanos , Antiparkinsonianos/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Levodopa/farmacologia , Levodopa , Selegilina/farmacologia , Selegilina , Antiparkinsonianos/farmacologia , Antiparkinsonianos , Amantadina/farmacologia , Amantadina , Pergolida/farmacologia , Pergolida , Bromocriptina/farmacologia , Bromocriptina , Triexifenidil/farmacologia , TriexifenidilRESUMO
1. The present work shows the results on behavior and on biochemical parameters of l-deprenyl (0.1, 5, and 10 mg/kg, p.o.) administered daily for 5 days to rats submitted to global cerebral ischemia. 2. The transient global ischemia was carried out by clamping the animals bilateral common carotid arteries for 20 min. The parameters studied were memory acquisition and memory retention, locomotor activity and thiobarbituric acid reactive substances, as an index of lipid peroxidation. 3. l-Deprenyl treatment significantly improved memory deficits as compared to the ischemic group as measured by the elevated T maze test. A similar result was observed on the passive avoidance test where l-deprenyl improved late but not early memory as compared to the ischemic group. Except for an increased locomotor activity observed in the group treated with 5 mg/kg, no other alteration was detected in this behavioral test. Rats submitted to transient global ischemia (and without l-deprenyl) showed an increase in MDA levels in the hippocampus and the treatment with l-deprenyl (5 or 10 mg/kg) significantly reversed this effect bringing values close to those of the sham-operated controls. A similar profile was observed with nitrite levels. 4. In conclusion, the work showed a significant protective effect of l-deprenyl on memory deficits and lipid hyperperoxidation observed after cerebral ischemia. Possibly, the drug is acting at least in part through its antioxidant activity.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Selegilina/farmacologia , Animais , Antioxidantes/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Peroxidação de Lipídeos/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Nitritos/antagonistas & inibidores , Nitritos/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The present study compared the antiimmobility effects of l-deprenyl (DEP) and moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an ethological approach. To investigate the degree of MAO-B inhibition by DEP and MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA) with DEP or with MOC were administered in three doses before immobility was tested in the forced-swimming paradigm. Tests were videotape recorded for analysis of the frequency and duration of the behaviors during the procedure. There was a significant, dose-dependent decrease in immobility duration and an increase in mobility duration of rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior composing 75% of the mobile behaviors. The intermediate doses of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and increased mobility. The antiimmobility effect of DEP was due to longer climbing behavior while MOC enhanced swimming duration. No behavioral changes were seen with the administration of the lower and higher doses of the MAOI. Potentiation of the antiimmobility effects was observed when ineffective doses of PHEA and of DEP or MOC were administered in combination. Differences between the MAO inhibitors on the active behaviors were also observed when administered with PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased swimming. This preclinical evaluation of selective MAO inhibitors indicates that both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly demonstrate that these antiimmobility effects are a consequence of increased brain concentrations of any one of the several monoamines implicated in the mechanism of action of DEP or MOC should be the subject of future studies.
Assuntos
Comportamento Animal/efeitos dos fármacos , Benzamidas/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Selegilina/farmacologia , Animais , Antidepressivos Tricíclicos/farmacologia , Imipramina/farmacologia , Masculino , Moclobemida , Atividade Motora/efeitos dos fármacos , Fenetilaminas/farmacologia , Psicotrópicos/farmacologia , Ratos , Ratos Wistar , NataçãoRESUMO
A doença de Parkinson foi descrita em 1817 e desde então os conhecimentos sobre sua patologia e formas de tratamento foram crescendo. A levodopaterapia constituiu um avanço significativo no tratamento sintomático desta doença. Os estudos sobre os possíveis mecanismos etiopatogênicos da doença de Parkinson (DP) formaram a base para proposição de um novo tipo de abordagem terapêutica: um tratamento possivelmente curativo ou neuroprotetor. Neste trabalho é feita uma revisão do uso do deprenil e tocoferol (Vit E) nas fases iniciais da DP. Os resultados mostraram que o tocoferol não apresentou efeito terapêutico e que o efeito do deprenil ainda não foi definido se neuroprotetor, sintomático ou ambos
Assuntos
Doença de Parkinson/terapia , Levodopa/farmacologia , Selegilina/farmacologia , Vitamina ERESUMO
The activities of monoamine oxidases, MAO-A and MAO-B, were separately determined in the cerebellum (CE) from adult rats neonatally exposed to 5 Gy X-irradiation. They were found to be markedly reduced: 58% and 66% of values from nonirradiated, littermate controls. Since the specific activities of both isoenzymes (per mg tissue weight) were not significantly different from controls, the reduction of activity per CE is basically explained by the irradiation-induced cerebellar atrophy. The unmodified MAO-A specific activity makes it highly improbable that the increase in the cerebellar noradrenaline content, characteristic of neonatally X-irradiated rats, could be due to a decreased neuronal metabolism of noradrenaline by this enzyme.
Assuntos
Cerebelo/enzimologia , Cerebelo/efeitos da radiação , Monoaminoxidase/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Cerebelo/citologia , Clorgilina/farmacologia , Feminino , Isoenzimas/metabolismo , Isoenzimas/efeitos da radiação , Masculino , Monoaminoxidase/efeitos da radiação , Inibidores da Monoaminoxidase/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/efeitos da radiação , Ratos , Ratos Wistar , Selegilina/farmacologiaRESUMO
The present work was addressed to study a possible relationship between monoamine oxidase (MAO) and the thyroid iodide transport mechanism. Normal rats treated with clorgyline (a selective MAO-A inhibitor) or tranylcypromine (a non-selective MAO inhibitor) showed a significantly diminished thyroid MAO activity, while deprenyl and pargyline (MAO-B inhibitors) did not modify the thyroidal enzyme activity with respect to the control group. Under these conditions, in vivo iodide transport was reduced both by clorgyline and tranylcypromine administration whereas it remained unchanged after treatment with MAO-B inhibitors. The effect of MAO inhibitors on thyroid MAO activity and in vivo iodide transport was also evaluated in rats treated with exogenous thyrotrophin (TSH) after endogenous TSH secretion blockade produced by T4 administration. In this condition, thyroid MAO activity was significantly lowered by clorgyline and was not modified by deprenyl. In contrast to the results observed in normal rats, in vivo iodide transport in TSH-treated rats remained unaltered after treatment either with clorgyline or deprenyl. MAO activity evaluated in bovine thyroid follicles in primary culture was highly sensitive to low concentrations of clorgyline (< 10 nmol/l) and relatively insensitive to deprenyl, a finding that indicates a predominance of the MAO-A isoform in the follicular cells in culture. When clorgyline (0.1 and 1 mumol/l) or deprenyl (1 mumol/l) were added to the culture medium, no modifications in the active transport of iodide were observed. These results indicate the absence of a direct linkage between thyroid MAO activity and the active iodide transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Iodetos/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Glândula Tireoide/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Clorgilina/farmacologia , Masculino , Técnicas de Cultura de Órgãos , Pargilina/farmacologia , Ratos , Ratos Wistar , Selegilina/farmacologia , Glândula Tireoide/efeitos dos fármacos , Tranilcipromina/farmacologiaRESUMO
O parkinsonismo idiopático (doença de Parkinson) e secundário, ou seja, que apresenta etiologia conhecida (pós-encefalítico, por toxinas, por drogas ou por algumas doenças degenerativas) såo processos neurodegenerativos que afetam progressivamente as funçÆes motoras normais do indivíduo. Neste trabalho, os aspéctos clínicos, etiológicos, fisiopatológicos e principalmente a descriçåo do arsenal farmacológico e as medidas utilizadas no combate ou retardo medicamentoso do parkinsonismo såo abordados e discutidos
Assuntos
Humanos , Amantadina/farmacocinética , Amantadina/farmacologia , Bromocriptina/farmacocinética , Bromocriptina/farmacologia , Carbidopa/farmacocinética , Carbidopa/farmacologia , Doença de Parkinson/etiologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Levodopa/farmacocinética , Levodopa/farmacologia , Selegilina/farmacocinética , Selegilina/farmacologiaAssuntos
Doença de Parkinson/tratamento farmacológico , Selegilina/farmacologia , Catalase/fisiologia , Dopamina/metabolismo , Interações Medicamentosas , Radicais Livres/metabolismo , Glutationa Peroxidase , Levodopa/farmacologia , Selegilina/administração & dosagem , Selegilina/história , Selegilina/toxicidade , Superóxido Dismutase/fisiologiaRESUMO
4-Dimethylaminophenethylamine (DMAPEA) was characterized as an MAO substrate. This compound was unaffected by MAO-A, while its oxidation by MAO-B was linear as a function of both time and enzyme concentration, with Km = 5.8 microM and Vmax = 21.2 pmol/min/mg protein, using a crude rat brain mitochondrial suspension as source of MAO. Both DMAPEA and its oxidation product, 4-dimethylaminophenylacetic acid (DMAPAA), can be detected electrochemically at 0.85 V. The high MAO-B affinity and selectivity of DMAPEA, together with its low oxidation potential, make this molecule a unique tool to determine MAO-B activity in a wide variety of tissue preparations using HPLC-ED.