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OBJECTIVE：To conduct reevaluation of systematic review/Meta-ana lysis on the efficacy and safety of selegiline in the treatment of Parkinson ’s disease （PD）. METHODS ：Retrieved from PubMed ，Embase，Cochrane L ibrary，CNKI，Wanfang database as well as official websites of domestic and foreign health technology assessment institutions ，based on manual retrieval and review of references ，systematic review/Meta-analysis on selegiline alone or combined with other anti-PD drugs （trial group ） versus placebo or blank control or other anti-PD drugs （control group ）were collected. The time limit was from database inception to November 2020. After literature screening and data extraction ，PRISMA statement was adopted to evaluate the quality of the included reports. AMSTAR 2 scale was used to evaluate the methodological quality ，and GRADE method was adopted to evaluate the evidence quality ，the outcome indicators of the included studies were summarised and analyzed. RESULTS ：A total of 12 systematic reviews/Meta-analysis were included ，involving 4 systematic reviews and 8 Meta-analysis；there were 31 outcome indexes in total. PRISMA scores of them ranged from 16.5 to 27.0，including 15.0 to 21.0 for 2 literatures（16.67％）and 22.0 to 27.0 for 10 literatures（83.33％）. Results of AMSTAR 2 scale showed that the methodological qualities of 2 literatures were classed as high quality ，3 as low quality and 7 as very low quality. Results of GRADE evidence quality evaluation showed that 1 evidence quality was high-level ，3 were medium-level ，5 were low-level ，21 were very low-level ，and 1 was no evaluable . The main factors leading to the degradation were bias risk （87.10％），publication bias （77.42％），inaccuracy （51.61％）and incon sistency（41.94％）. In terms of therapeutic efficacy ，compared with control group ，selegiline could improve the total score of UPDRS ，UPDRS Ⅰ score，UPDRS Ⅱ score，UPDRS Ⅲ score and Webster score in patients with Parkinson ’s disease，either monotherapy or in combination with other anti-PD drugs （P＜0.05）. In terms of safety ，there was no significant difference in the incidence of adverse events or mortality between 2 groups（P＞0.05），but the rate of withdrawal due to adverse events was higher（P＜0.05）. CONCLUSIONS ：Selegiline is effective and safe in the treatment of Parkinson ’s disease ，but current methodological quality and evidence quality of included systematic reviews /Meta-analysis are low，which requires further standardization of research methods.
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Selegiline HCl is an irreversible MAO-B inhibitor used to reduce symptoms in early-stage Parkinson’s disease. It isused as an adjunct to drugs, such as L Dopamine (L-DOPA). The present study is designed to develop and validatea rapid, sensitive, and straightforward separation method with Electrospray ionization and triple quadrupole massanalyzer for the quantification of Selegiline HCl in bulk and pharmaceutical formulation. Zorbax C18 column (50 mm× 4.6 mm i.d, 5 µ particle size) was used for the separation of analyte and internal standard. The samples were elutedusing 0.1% Formic acid in water and Methanol (40:60%v/v) which is delivered at 0.5 ml/minute flow rate, with achromatographic runtime of 5 minutes. The eluents were monitored using a tandem mass spectrometer equipped withan electrospray ionization in positive mode and a triple quadrupole mass analyzer. The detection was carried out inmultiple reaction-monitoring mode by quantifying the m/z 188.05→91.10 ion transition pair; with collision energy−29.0 V for Selegiline HCl. Linearity was achieved over the concentration range 3.5–6.5 ng/ml for the developedmethod. The limit of detection and limit of quantification were found to be 0.2 and 0.5 ng/ml, respectively. Thecorrelation coefficient (r2) value was ≥0.9985 for Selegiline HCl. This method offers a sensitive quantification ofSelegiline HCl in the pharmaceutical formulation.
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OBJECTIVE ① To estimate the value of the subacute MPTP mouse model in aspects of behavioral performance, biochemical changes and pathological abnormalities. ② To find effective positive drugs. METHODS Male C57BL/6 mice were injected with MPTP (30 mg·kg- 1 ·d- 1, ip) for 5 consecutive days. Three days before MPTP injection, the mice were orally administered selegiline (3 mg·kg-1·d-1), pramipexole (3 mg·kg-1·d-1), or medopar (100 mg·kg-1·d-1) for 18 d. Behavioral perfor?mance was assessed in the open field test, pole test and rotarod test. Neurotransmitters in the striatum were detected using HPLC. Protein levels were measured by Western blot. Pathological characteristics were examined by immunohistochemistry. Ultrastructure changes were observed by electron microscopy. RESULTS The subacute MPTP treatment did not induce evident motor defects despite severe injuries in the dopaminergic system. Additionally, MPTP significantly increased the α-synuclein levels and the number of astrocytes in the striatum, and destroyed the blood-brain barrier (BBB) in the substantianigra pars compacta. Both selegiline and pramipexole were able to protect the mice against MPTP injuries. CONCLUSION The subacute MPTP mouse model does not show visible motor defects; it is not enough to evaluate the validity of a candidate just based on behavioral examination, much attention should also be paid to the alterations in neurotransmitters, astrocytes, α- synuclein and the BBB. In addition, selegiline or pramipexole is a better choice than medopar as an effective positive control for the subacute MPTP model.
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Objective To study the content variation of selegiline and its metabolites in urine, and based on actual cases, to explore the feasibility for the identification of methamphetamine abuse and selegiline use by chiral analysis. Methods The urine samples were tested by chiral separation and LC-MS/MS method using CHIROBIOTICTM V2 chiral liquid chromatography column. The chiral analysis of metham-phetamine and amphetamine were performed on the urine samples from volunteers of selegiline use and drug addicts whom suspected taking selegiline. Results After 5 mg oral administration, the positive test time of selegiline in urine was less than 7 h. The mass concentrations of R(-)-methamphetamine and R(-)-amphetamine in urine peaked at 7 h which were 0.86μg/mL and 0.18μg/mL and couldn't be de-tected after 80 h and 168 h, respectively. The sources of methamphetamine and amphetamine in the urine from the drug addicts whom suspected taking selegiline were analysed successfully by present method. Conclusion The chiral analysis of methamphetamine and amphetamine, and the determination of selegi-line's metabolites can be used to distinguish methamphetamine abuse from selegiline use.
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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.
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Parkinson Disease/therapy , Nanoparticles , Selegiline/analysis , Chemistry, Pharmaceutical , Chitosan/analysis , Drug LiberationABSTRACT
Objective: To observe the effects of selegiline on tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) in the gastric antrum of rats with Parkinson disease (PD), so as to investigate the therapeutic effect and mechanism of selegiline for treatment of gastric disfunction in PD. Methods: A total of 72 SD rats were randomly divided into normal control group, PD model group, and selegiline treatment group. PD rat models were established by subcutaneous rotenone injection. After the success of model preparation, PD group was given normal saline, and the therapy group was given selegiline (0.5 mg/kg) by intragastric administration. At 4 d and 8 d after therapy, residual rate of solid food was detected in the stomachs of animals, and the expressions of TH and nNOS were detected by immunohistochemistry method and Western blotting analysis. Results: Compared with the control group, the model group had significantly higher residual rate of solid food, significantly lower TH expression, and significantly increased nNOS expression in the gastric antrum (allP<0.01). Compared with the model group, the treatment group had significantly decreased residual rate of solid food, significantly increased TH expression and significantly lower nNOS expression in the gastric antrum at all time points (P<0.05, or P<0.01). At 8 days after selegiline treatment, the residual rate of solid food was significantly lower, TH expression was significantly increased, and nNOS expression was significantly decreased (all P<0.05) compared with those at 4 days after treatment. Conclusion: Selegiline can improve the gastric dysfunction in PD rats, which might be related to relieve of gastric dopaminergic neuronal injury and inhibition of nNOS expression.
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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.
Subject(s)
Acetylcholine , Alzheimer Disease , Antidepressive Agents , Depression , Freezing , Handling, Psychological , Head , Indans , Iron , Levodopa , Moclobemide , Monoamine Oxidase , Monoamine Oxidase Inhibitors , Parkinson Disease , Phenelzine , Selegiline , TranylcypromineABSTRACT
Objective To determine the prescription of selegiline transdermal patches.Methods The selegiline transdermal patches were prepared and the ingredient amount of selegiline transdermal patches was determined according to the orthogonal design.Results The best prescription of selegiline transdermal patches：3%selegiline,3%Azone,15%RS100,60%PSA.Conclusion Selegiline is suitable for the transdermal therapeutic systems.Orthogonal design of prescription was suitable to study selegiline transdermal patches.
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OBJECTIVE:To investigate the possible mechanism of the neuroprotective action of isatin(ISA).METHODS:A total of 40 C57BL/6J mice were divided into 4 groups:control group,model group,ISA(200 mg?kg-1 intragastrically) group,and selegiline(0.5 mg?kg-1 intraperitoneally) group.After pretreatment with drugs for 10 days,the latter 3 groups were given 1-methyl-4-phenyl-1,2,3,6-tetrahyrdropyridine(MPTP) intraperitoneally to establish Parkinson's disease(PD) model,then the mice were put to death for the determination of the activities of MAO-B,SOD and GSH-px in blood serum and brain tissue.RESULTS:As compared with blank control group,the activity of MAO-B in model group increased slightly,while the activities of SOD and GSH-px decreased(P
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@# Objective To assess the clinical efficacy and safety of amantadine monotherapy and concomitant amantadine with salvia miltiorrhiza compound or selegiline of the treatment of Parkinson's disease.Methods The clinical trial was performed in the multicenter, open label study. Amantadine group: 35 cases, amantadine plus salvia miltiorrhiza compound group: 34 cases and amantadine plus selegiline group: 29 cases. The clinical efficacy had been assessed with modified Webster scale (WR) and motor dysfunction rating scale for Parkinson's disease (MDRSPD) with interval of two months for one year. The safety data included blood glucose, hepatic and renal function tests, blood and urine routine tests.Results The clinical improved rates were 42.9% (WR) and 37.1% (MDRSPD) in amantadine group, respectively. The clinical score was improved in 34.2% (WR) and 26.5% (MDRSPD) in amantadine plus salvia miltiorrhiza compound group, respectively. The clinical improvement was 51.1% (WR)and 48.3% (MDRSPD) in amantadine plus selegiline group, respectively. There were no significant differences among these three groups (t-test,P>0.05). The clinical marked efficacy rates in assessment of MDRSPD were 2.8% in amantadine group, 11.8% in amantadine plus salvia miltiorrhiza compound group and 27.6% in amantadine plus selegiline group, respectively. There was significant difference between amantadine group and amantadine plus selegiline group, but no significant difference between amantadine group and amantadine plus salvia miltiorrhiza compound group. The adverse event rates were 27.8% in amantadine group, 8.8% in amantadine plus salvia miltiorrhiza compound group and 31.0% in amantadine plus selegiline group, respectively. All these events were mild, of short duration and resolved without treatment. Conclusion There was some efficacy rate in all three groups. Comparing with amantadine group, there was higher marked efficacy rate in amantadine plus selegiline group.
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Objective To study the efficacy and safety of selegiline in the treatment of patients with Parkinson's disease (PD) at early stage. Methods The randomized and blank controlled study was performed. Sixty PD patients at early stage who had been treated with trihexyphenidyl, amantadine and vitaminE were divided into two groups. One was added to selegiline hydrochloride (5 mg/d) for eight weeks, the other was blank controlled group. Efficacy of selegiline in each patient was evaluated by modified Webster scale. Tolerance and adverse effects were also observed.Results After four and eight weeks, the score of modified Webster scale of selegiline group was lower than that before selegiline treatment (all (P