Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson's therapy: a novel approach

The objective of the research was to formulate and evaluate selegiline hydrochloride loaded chitosan nanoparticles for the Parkinson's therapy in order to improve its therapeutic effect and reducing dosing frequency. Taguchi method of design of experiments (L9 orthogonal array) was used to get optimized formulation. The selegiline hydrochloride loaded chitosan nanoparticles (SHPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and tween 80 as surfactant. The SHPs had a mean size of (303.39 ± 2.01) nm, a zeta potential of +32.50mV, and entrapment efficiency of SHPs was 86.200 ± 1.38%. The in vitro drug release of SHPs was evaluated in phosphate buffer saline (pH 5.5) using goat nasal mucosa and found to be 82.529% ± 1.308 up to 28 h. Release kinetics studies showed that the release of drug from nanoparticles was anomalous (non-fickian) diffusion indicating the drug release is controlled by more than one process i.e. superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. SHPs showed good stability results as found during stability studies at different temperatures as mentioned in ICH guidelines. The results revealed that selegiline hydrochloride loaded chitosan nanoparticles are most suitable mode of delivery of drug for promising therapeutic action.

O objetivo da pesquisa foi formular e avaliar nanopartículas de quitosana contendo cloridrato de selegilina para terapia do Parkinson, a fim de melhorar o seu efeito terapêutico e reduzir a frequência de dosagem. Método de Taguchi, de planejamento experimental, (L9 matriz ortogonal) foi usado para obter a formulação otimizada. As nanopartículas de quitosana contendo cloridrato de selegilina (PCHs) foram preparadas por gelificação iônica de quitosana com ânions tripolifosfato (TPP) e Tween 80 como tensoativo. As PCHs apresentaram tamanho médio de (303.39 ± 2,01) nm, potencial zeta de +32.50 mV e eficiência de encapsulação de 86.200±1,38%. A liberação do fármaco in vitro foi avaliada em solução salina de tampão fosfato (pH 5,5), usando a mucosa nasal de cabra e o resultado encontrado foi de 82.529% ± 1.308, acima de 28 h. Estudos de cinética de liberação mostraram que a liberação do fármaco das nanopartículas foi por difusão anômala (não fickiana), indicando que é controlada por mais de um processo, ou seja, a superposição dos fenômenos de difusão controlada e intumescimento. As PCHs mostraram resultados de boa estabilidade, encontrada durante os estudos de estabilidade em temperaturas diferentes, como mencionado em diretrizes do ICH. Os resultados revelaram que o sistema de nanopartículas de quitosana contendo cloridrato de selegilina é o mais adequado sistema de liberação de fármacos de ação terapêutica promissora.

New Evidences of Neurotoxicity of Aroclor 1254 in Mice Brain: Potential of Coenzyme Q10 in Abating the Detrimental Outcomes

OBJECTIVES: The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10) in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. METHODS: Biochemical estimations of brain lipid peroxidation (LPO), reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetyl cholinesterase (AChE), and histopathological investigations of brain tissue were carried out. RESULTS: Oral exposure of aroclor 1254 (5 mg/kg) led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]). This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP) which served as a reference standard. CONCLUSIONS: Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

Transplantation of deprenyl-induced tyrosine hydroxylase-positive cells improves 6-OHDA-lesion rat model of Parkinson's disease: behavioral and immunohistochemical evaluation

There is longstanding experimental and clinical evidence that supports the idea that replacement of dopaminergic [DAergic] neurons can ameliorate functional disabilities of Parkinson's disease [PD]. The purpose of the present study is to examine the efficacy of transplantation of rat bone marrow stromal cell [BMSCs]-derived tyrosine hydroxylase-positive [TH[+]] cells induced by deprenyl into 6-hydroxydopamine [6-OHDA]-lesioned rat models, using behavioral tests and immunohistochemical evaluations. In this experimental study, undifferentiated BrdU-labeled BM-SCs were incubated in serum-free medium that contained 10[-8] M deprenyl for 24 hours. Afterwards, BMSCs were cultured for 48 hours in alpha-minimal essential medium [alpha-MEM] supplemented with 10% FBS, then differentiated into Th[+] neurons. We randomly divided 24 hemiparkinsonian rats as follows: group 1 [control] received only medium, while groups 2 and 3 were injected with 2x10[5] BMSCs and deprenyl-treated cells in 4 microl medium. Injections were made into the injured strata of the rats. Rotational behavior in response to apomorphine was tested before transplantation and at 2, 4, and 6 weeks post-graft. Animals were then sacrificed, and the brains were extracted for immunohistochemical and electron microscopic studies. Apomorphine-induced rotation analysis indicated that animals with grafted cells in groups 2 and 3 exhibited significantly less rotational behavior than those in the control group at 2, 4, and 6 weeks after transplantation. Immunohistochemical analysis demonstrated that BrdU-labeled cells expressed specific neuronal markers, such as NF 200 and TH, at the implantation site. The presence of TH[+] cells in conjunction with the reduction in rotation might show the capacity of grafted cells to release dopamine. Ultrastructural analysis revealed the presence of immature neurons and astrocyte-like cells at the graft site. Th[+] neurons induced by deprenyl can be considered as a cell source for PD autograft therapy?

Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K

Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine beta-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 microM, and 43.9 microM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 microM, and 42.5 microM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 microM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 microM and this value was higher than that of deprenyl (0.046 microM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 microM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

[Inductive effect of deprenyl and dimethyl sulfoxide on proliferation and survival of the mesenchymal stem cells]

Research have been focused on the applying the chemical inducer for transdifferentiation the adult BMSCs into neural cell. So that, at the first should investigate the toxcity effect of the chemical inducer on the induced cells. Plasticity and easy accessibility of bone marrow mesenchymal stem cells is a unique charactristic for treatment of neural disorderies. This study was desgined to determine the inductive effect of Deprenyl and Dimethyl sulfoxide on proliferation and survival of the mesenchymal stem cells. In this experimental study, BMSCs isolated from the adult rat bone marrow and cultured in alpha MEM containing 10% FBS. Cell identity for surface antigens was performed in third passage by immunocytochemistry and multipotancy capacity of BMSCs was done by BMSC differentiation into adipocytes and osteocytes. The cells were exposed to chemical agents [a: the alpha MEM medium supplemented with 2% DMSO, b: the alpha MEM medium supplemented with 10[-8]M Deprenyl] for 24 hours and then transferred to alpha MEM containing 10% FBS cell survival and proliferation was evaluated after the 24, 48, 72 and 96 houres by MTT [3-[4-5-Dimethylthiazolyl-2-y1]-2,5-diphenyltetrazolium romid] test. Data were analyzed using SPSS-16, One-Way ANOVA and Tukey tests. In addition to expression the surface antigens and adipogenic and osteogenic differentiation by BMSCs, MTT test results showed that proliferation and survival of induced-deprenyl and DMSO cells within 48, 72 and 96 hours after the induction was increased significantly than negative control group. Deprenyl increases survival and cell proliferation compared to Dimethyl Sulfoxide. It can be used as cell inducer

MAO-inhibitors in Parkinson's Disease

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.

Comparison of the Effect of Glutamate; Oxyferriscorbone and Deprenyl on Parkinsonian Syndrome

Background: Patients with Parkinson's disease (PD) show a dramatic increase in their brain iron content has suggested the role of iron in degeneration of dopaminergic nigrostriatal neurons in PD. Several studies have described the association of high dietary iron and PD. However; the role of iron the pathogenesis of PD is still hotly debated. Objective: The purpose of this study was to investigate the effects of L-glutamate; oxyferriscorbone (OFC) and L-Deprenyl on parkinsonian syndrome (PS) in rats. Methods: This study was performed on 244 male non-strain rats (250-270g;-10 wk old). By intranigral bilateral administration of 1-Methyl-4-phenylpyridinium ion (MPP+) (10?g/2?/l into each side) and 6-hydroxydopamine (6-OHDA) (12?g/3?l; Sigma; into each side ) in rats was induced the dopamine deficient model of PS (DDPS) and the cholinergic model (ChPS) in rats produced by intracaudate injection of acetylcholine (5?g/2?l each side ) with neostigmine (1?g/1?l each side). These models were then used to investigate the effects of L-glutamate; OFC and L-Deprenyl on PS and the electric activity (EA) of the sensorimotor cortex; caudate nuclei; ventrolateral nuclei of the thalami; and substantia nigra in rats. Results: Intracaudate injection of L-glutamate (100?g/3?l; into each side) enhanced bradykinesia; rigidity and produced a weak tremor in the DDPS. This effect was more pronounced in ageing (12 months) rats and in some of them; we observed orofacial dyskinesia. In the ChPS; L-glutamate enhanced tremor and bradykinesia. The single and repeated injection of OFC (5; 7; 5; 15 and 20 mg/rat; intraperitioneally; i.p.) did not produce a statistically significant change of PS in both models. L-deprenyl (5; 10 and 20 mg/kg; i.p.) dose-dependently reduced bradykinesia and rigidity in the DDPS; whereas increased tremor and failed to decrease bradykinesia and rigidity in the ChPS. Conclusion: This study indicates that glutamate aggravates PS in both models. OFC does not have any effect on PS. Deprenyl has antiparkinsonian effect in the DDPS; but not in the ChPS

Protective potential of deprenyl in paraquat-induced nephrotoxicity in rats

Deprenyl, a selective and irreversible monoamine oxidase B [MAO-B] inhibitor, has various pharmacological effects unrelated to MAO-B inhibition including antioxidant ones. Paraquat [PQ], a well known herbicide, causes severe nephrotoxicity mediated by redox-cycling and extensive production of superoxide anions in the kidney. The kidney is a primary site for PQ toxicity as it is the main organ of its excretion. Consequently, the possible protective effects of deprenyl [10 mg/kg, i.p.] against nephrotoxicity induced by long-term administration of PQ in rats were examined. PQ was intraperitoneally injected once weekly [20 mg/kg] with or without daily injections of deprenyl for 6 successive weeks. Nephrotoxicity was assessed by measuring serum levels of creatinine, urea nitrogen and uric acid as well as histological examination of kidney sections. Changes in renal oxidant status were monitored by measurements of reduced glutathione [GSH] content and that of thiobarbituric acid reactive substances [TBARS], an index of renal lipid peroxidation. In addition, determination of total nitrate/nitrite [NOx] content, which reflects nitric oxide [NO] content of renal tissues, was performed. Finally, changes in renal enzymatic activities of lactate dehydrogenase [LDH], superoxide dismutase [SOD] and myeloperoxidase [MPO] were also measured. PQ administration resulted in marked nephrotoxicity manifested by severe increase in serum creatinine and urea nitrogen levels accompanied by changes in renal oxidant status of rats demonstrated by elevated TBARS content and increased activities of MPO and SOD. It also resulted in depletion of renal GSH and NOx contents as well as reduced activity of cytosolic LDH. However, no significant effect was noted on serum uric acid level. Six weeks of regular daily treatment with deprenyl significantly protected against most of PQ-induced biochemical changes evidenced by lowering of elevated creatinine level and reduction of elevated TBARS content and MPO activity. Deprenyl also attenuated PQ-induced depletion of GSH and NOx contents. On the other hand, deprenyl failed to ameliorate PQ-induced effects on serum urea nitrogen level or on kidney cytosolic LDH and SOD activities. Histological examinations of kidney sections revealed marked lesions with PQ especially in renal proximal tubules and fair protection by deprenyl. It could be concluded that deprenyl offered remarkable protection against PQ-induced nephrotoxicity in rats which could expand its use in other areas outside the central nervous system

Quality of life in Parkinson's disease--Indian scenario.

The subjective sense of well being is central to the concept of quality of life (QoL) and a good QoL should be the ultimate goal to any therapeutic measure. In Parkinson's disease (PD), several rating scale are in vogue to measure the QoL, namely PDQ-39, PDQ-8, SF-36, Likert scale etc. Parkinson's Impact Scale (PIMS) has been used in this study to assess the QoL which includes 10 items. METHODOLOGY: Thirty two patients of Parkinson's disease satisfying the UK Parkinson's disease brain bank diagnostic criteria, ranging from HY stage I to IV have been recruited. UPDRS was also administered to them. Statistical analysis was performed using Spearman rank correlation and multivariate stepwise regression analysis using SPSS for windows. RESULT: Seventy two percents were male, all getting levodopa, 72% got anticholinergics. Monthly income varied from Rs.800 (US dollars 17.10) to Rs.15,000 (US dollars 320) pm. Eighty eight percent belonged to HY II-III. UPDRS score ranged from 3-85 (40.4 +/- 18.6). PIMS total score ranged from 1-22 (10.4 +/- 6.1). DISCUSSION AND CONSLUSION: The QoL deteriorates with H-Y staging, the UPDRS score, not with advancing age as seen in other studies. It is also significantly influenced by duration of the disease and financial security. Surprisingly, the family and community relations were not significantly affected with advancing disease, perhaps due the close family and social tie up among Indians. So, measurement of QoL should be made an essential part to the routine assessment of PD patients to get a complete scenario of the problem. PIMS can serve as a comprehensive tool for the same suitable for use in the OPD.

Monoamine Oxidase Inhibitors Attenuate Cytotoxicity of 1-Methyl-4-phenylpyridinium by Suppressing Mitochondrial Permeability Transition

Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (non-selective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with 500 micrometer MPP+. The MAO inhibitors at 10 micrometer revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of MPP+ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.

Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells

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 æM) 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 æM) and ascorbic acid (100 æM) did not attenuate the effects of dopamine. Selegiline (10 æM) 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.

Fármacos antiparkinsonianos / Anti-Parkinson drugs

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

Terapia neuroprotectora de la Enfermedad de Parkinson / Neuroprotective therapy in Parkinson's Disease

With the current limitations on treating Parkinsonãs disease, neuroprotection should be looked at as a possible way of slowing the varying processes involved in the onset of the disease. A review was made of the work of NINDS experts, who evaluated 59 drugs resulting from their Medline and Pub Med search. Twelve drugs, those considered the most promising, were included in the final analysis. We look at such substances as caffeine, coenzyme q10, estrogens, minocycline, nicotine, rasagiline-selegiline, and ropinirole-pramipexole. These agents acted dissimilarly, but favorably, on some of the diseaseãs processes or on its underlying pathogenesis, although the mechanisms involved and the duration of the beneficial effects were not clear. The challenge is to overcome the difficulties that make the results of the few current studies uncertain, using new methods, such as transgenic models, to maintain hope for effective future treatments.

Studies on anticonvulsant actions of L-deprenyl.

L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.

Effect of selegiline on cognitive functions in Parkinson's disease.

BACKGROUND: Selegiline hydrochloride, a selective MAO-B inhibitor is known to improve motor functions in Parkinson's disease (PD). The present study was undertaken to study the effect of selegiline on memory and intelligence of PD patients. MATERIAL AND METHOD: Thirty two patients of PD were divided in two groups: selegiline group (n = 17) received 10 mg selegiline per day and control group (n = 15) did not receive selegiline. Patients receiving trihexyphenidyl and selegiline were excluded. All other treatment remained unchanged. All patients were examined at baseline and after three months for change in UPDRS score, WAIS score, memory test and P300. RESULTS: Patients in selegiline group had less severe disease (UPDRS score 24.11 +/- 14.07) as compared to controls (UPDRS score 40.53 +/- 18.52). There was significant improvement in UPDRS score (p < 0.05), WAIS (p < 0.001) and memory (p < 0.001) in selegiline group. In the control group there was a significant prolongation of P300 latency (p < 0.05). CONCLUSION: The study suggests that selegiline improves memory functions and intelligence in PD patients in addition to motor functions. It also prevents prolongation of P300 latency which is a marker of cognitive function.

Escolha do tratamento da narcolepsia / The treatment of narcolepsy

O tratamento da narcolepsia visa seus dois sintomas principais, a sonolência excessiva diurna e a cataplexia. A primeira é usualmente controlada com anfetmina, metilfenidato e pemoline. Mais recentemente, inibidores da MAO, e principalmente os inibidores seletivos de MAO-A e B têm mostrado resultados promissores, com a selegilina. Modafinil, um estimulante alfa-1-adrenérgico tem também evidenciado bons resultados. A cataplexia, por sua vez, é geralmente tratada com antidepressivos tricíclicos. Dentre as novas drogas, sem efeito colateral antropínico, temos o hidrocloreto de viloxazina, um bloqueador de recaptaçäo da noradrenalina

Tratamento neuroprotetor da doença de Parkinson / Neuroprotector treatment of Parkinson's disease

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