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1.
Rev. neurol. (Ed. impr.) ; 71(11): 407-420, 1 dic., 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198940

RESUMO

INTRODUCCIÓN: Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. DESARROLLO: Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. CONCLUSIÓN: El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motora


INTRODUCTION. Motor fluctuations are one of the most common complications of Parkinsons disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT. Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION. The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations


Assuntos
Humanos , Consenso , Técnica Delfos , Doença de Parkinson/tratamento farmacológico , Transtornos Motores/tratamento farmacológico , Transtornos Motores/fisiopatologia , Doença de Parkinson/fisiopatologia , Levodopa/uso terapêutico , Dopaminérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Estimulação Encefálica Profunda
2.
Psychiatr Danub ; 32(Suppl 1): 139-141, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32890377

RESUMO

In this brief report we present the case of a 53 year old man with a very debilitating Generalized Anxiety Disorder successfully treated with tranylcypromine. After several failed treatment attempts following international guidelines recommendations over the course of one year and a half, tranylcypromine was prescribed which led to effective and sustained remission of anxiety symptoms for this patient. We also briefly explore treatment options for resistant cases of generalized anxiety disorder, given the major negative impacts of untreated GAD in a person's daily functioning and quality of life.


Assuntos
Transtornos de Ansiedade , Inibidores da Monoaminoxidase , Qualidade de Vida , Ansiedade , Transtornos de Ansiedade/tratamento farmacológico , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/uso terapêutico
3.
Fortschr Neurol Psychiatr ; 88(9): 620-633, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32588409

RESUMO

Inhibitors of COMT and MAO-B are well established in the pharmacotherapy of Parkinson's disease (PD). MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Both classes of compounds prolong the response duration of levodopa and optimise its clinical benefit. As a result, the ON-times are prolonged significantly. In the past, MAO-B inhibitors were also adminstered for neuroprotection; however, despite convincing scientific reasoning in support of neuroprotective effects, these could not be substantiated in clinical studies performed so far.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Catecol O-Metiltransferase/metabolismo , Humanos , Levodopa/uso terapêutico , Monoaminoxidase/metabolismo
4.
Curr Pharm Des ; 26(4): 509-516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32003681

RESUMO

With respect to the total cure failure of current drugs used in the treatment of neurodegenerative diseases, alternative strategies are followed. Particularly, neuroprotection approaches are questioned. Metal chelation, antioxidant towards oxidative stress, modulation of the amyloidogenic pathway, MAO-B inhibition, and NMDA receptor antagonism is more or less typical examples. Some of the representative drug candidates with promising neuroprotective features are assessed in clinical trials. Although initial attempts were found hopeful, none of the candidates have been found successful in each required clinical trials, particularly depending on the failures in terms of cognitive enhancement and slowing the progressive characteristics of neurodegenerative diseases. Today, neuroprotection is evaluated using multi-target ligand-based drug design studies. Within this study, the clinical outcomes of these studies, the rationale behind the design of the molecules are reviewed concomitant to the representative drug candidates of each group.


Assuntos
Doença de Alzheimer , Neuroproteção , Fármacos Neuroprotetores , Doença de Parkinson , Doença de Alzheimer/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
5.
J Med Chem ; 63(3): 1361-1387, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31917923

RESUMO

The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis- and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores da Monoaminoxidase/uso terapêutico , Piperidinas/uso terapêutico , Estirenos/uso terapêutico , Animais , Antidepressivos/síntese química , Antidepressivos/metabolismo , Encéfalo , Domínio Catalítico , Humanos , Isoenzimas/antagonistas & inibidores , Cinética , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monoaminoxidase/química , Monoaminoxidase/classificação , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/metabolismo , Piperidinas/síntese química , Piperidinas/metabolismo , Ligação Proteica , Estereoisomerismo , Relação Estrutura-Atividade , Estirenos/síntese química , Estirenos/metabolismo
6.
J Clin Psychopharmacol ; 40(1): 63-74, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31834088

RESUMO

PURPOSE: We conducted a comprehensive meta-analysis of the comparison of tranylcypromine (TCP) and tricyclic antidepressants (TCAs) in the treatment of depression because such work is lacking in medical scientific literature. METHODS: Literature was searched for studies of TCP controlled by TCAs in multiple databases and in reviews of TCP and monoamine oxidase inhibitors. The natural logarithm of the odds ratio (logOR) and the pooled logOR according to a fixed effect model were calculated for the numbers of responders and nonresponders. RESULTS: A total of 227 studies of TCP were found including 75 controlled studies of TCP-monotherapy. Twelve of 23 studies of TCP monotherapy and TCAs were excluded for several reasons (duplicates, safety studies, retrospective, cross-over), leaving 11 prospective and parallel controlled studies of TCP monotherapy versus TCAs (6 randomized double-blind). One study was excluded from the meta-analysis because of low quality of study design according to the Food and Drug Administration guidelines of studies of antidepressant drugs and high risk of bias according to the Cochrane's tool. Two studies with equal efficacy of TCP and TCAs in continuous endpoints did not provide dichotomous response data. A pooled logOR of 0.480 (95% confidence interval, 0.105-0.857, P = 0.01) resulted for the remaining eight studies in the primary meta-analysis, which favors TCP significantly over TCAs (test for heterogeneity: Х = 8.1, df = 7, P > 0.3, not heterogenous; I = 13.6%, heterogeneity not important). The result is robust with respect to inclusion of hypothetical response data of the 2 studies with continuous data only: pooled logOR, 0.350 (95% confidence interval, 0.028-0.672, P = 0.03). Visual inspection of forest plots and subgroup analysis suggest that superiority of TCP over TCAs is determined by 2 studies in psychomotor-retarded (anergic) depression. CONCLUSIONS: Tranylcypromine and TCAs have an equal antidepressant effect in a mean sample of depressed patients with mixed psychomotor symptoms. Tranylcypromine might be superior to TCAs in depression with predominant psychomotor retardation.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos Tricíclicos/uso terapêutico , Depressão/tratamento farmacológico , Inibidores da Monoaminoxidase/uso terapêutico , Tranilcipromina/uso terapêutico , Adulto , Idoso , Antidepressivos Tricíclicos/efeitos adversos , Depressão/diagnóstico , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/efeitos adversos , Desempenho Psicomotor/efeitos dos fármacos , Tranilcipromina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
9.
Biomedica ; 39(3): 491-501, 2019 09 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31584763

RESUMO

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.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson Secundária/tratamento farmacológico , Animais , Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Catalepsia/induzido quimicamente , Cumarínicos , Modelos Animais de Doenças , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Haloperidol , Levodopa/administração & dosagem , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Inibidores da Monoaminoxidase/administração & dosagem , Doença de Parkinson Secundária/induzido quimicamente , Reserpina/administração & dosagem
10.
CNS Neurol Disord Drug Targets ; 18(8): 643-654, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550216

RESUMO

BACKGROUND: Chalcones are considered as the selective scaffold for the inhibition of MAO-B. OBJECTIVES: A previously synthesized ethyl acetohydroxamate-chalcones (L1-L22) were studied for their inhibitory activities against human recombinant monoamine oxidase A and B (hMAO-A and hMAO-B, respectively) and acetylcholinesterase (AChE) as multi-target directed ligands for the treatment of Alzheimer's Disease (AD). METHODS: Enzyme inhibition studies of MAO-A, MAO-B and AChE is carried out. Computational studies such as Molecular docking, Molecular Mechanics/Generalized Born Surface Area calculations, ADMET prediction, and protein target prediction are also performed. RESULTS: Among the screened compounds, compound L3 has most potent hMAO-B inhibition with an IC50 value of 0.028 ± 0.0016 µM, and other compounds, L1, L2, L4, L8, L12, and L21 showed significant potent hMAO-B inhibition with IC50 values of 0.051 ± 0.0014, 0.086 ± 0.0035, 0.036 ± 0.0011, 0.096 ± 0.0061, 0.083 ± 0.0016, and 0.038 ± 0.0021 µM, respectively. On the other hand, among the tested compounds, compound L13 showed highest hMAO-A inhibition with an IC50 value of 0.51± 0.051 µM and L9 has a significant value of 1.85 ± 0.045 µM. However, the compounds L3 and L4 only showed high selectivities for hMAO-B with Selectivity Index (SI) values of 621.4 and 416.7, respectively. Among the substituents in ring A of ethyl acetohydroxamate-chalcones (L1-L9), F atom at p-position (L3) showed highest inhibitory effect against hMAO-B. This result supports the uniqness and bizarre behavior of fluorine. Moreover, chalcones L3, L4, L9, L11, and L12 showed potential AChE inhibitory effect with IC50 values of 0.67, 0.85, 0.39, 0.30, and 0.45 µM, respectively. Inhibitions of hMAO-B by L3 or L4 were recovered to the level of the reversible reference (lazabemide), and were competitive with Ki values of 0.0030 ± 0.0002 and 0.0046 ± 0.0005 µM, respectively. Inhibitions of AChE by L3 and L11 were of the competitive and mixed types with Ki values of 0.30 ± 0.044 and 0.14 ± 0.0054 µM, respectively. CONCLUSION: The studies indicated that L3 and L4 are considered to be promising multitarget drug molecules with potent, selective, and reversible competitive inhibitors of hMAO-B and with highly potent AChE inhibitory effect.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Chalconas/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Monoaminoxidase/metabolismo , Relação Estrutura-Atividade
11.
Tijdschr Psychiatr ; 61(7): 498-503, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31372971

RESUMO

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Lítio/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Antidepressivos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
J Psychiatr Pract ; 25(4): 290-297, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31291209

RESUMO

This column is the sixth in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first 3 columns in this DDI series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs, how to recognize such DDIs, strategies for avoiding and/or minimizing adverse outcomes from such DDIs, and pharmacokinetic considerations concerning DDIs in psychiatric practice. The fourth and fifth columns in this series presented a pair of parallel tables, one of which outlined the primary, known mechanism(s) of action of all commonly used psychiatric medications and one of which summarized major types of pharmacodynamic DDIs based on mechanism of action. Clinicians can use these 2 tables together to predict pharmacodynamically mediated DDIs. This sixth column in the series discusses some key issues related to pharmacodynamic interactions involving commonly used psychiatric medications. The column first discusses 3 types of pharmacological agents that deserve special mention because of the widespread types of pharmacodynamic DDIs they can have with psychiatric and other medications: ethanol, opioids, and monoamine oxidase inhibitors, with a special focus on hypertensive crises and serotonin syndrome with monoamine oxidase inhibitors. The column also discusses DDIs in terms of effects on the cardiovascular system, including QTc prolongation, blood pressure and heart rate regulation, increased risk of bleeding and abnormal bleeding, and valvular heart disease, and on the central nervous system, including increased sedation, respiratory depression, body temperature regulation, and tardive dyskinesia. The overall goal of this series of columns is to present a simple way of conceptualizing neuropsychiatric medications in terms of their pharmacodynamics and pharmacokinetics to allow prescribers to take these facts into consideration when they need to use more than 1 drug in combination to optimally treat a patient.


Assuntos
Transtornos Mentais/tratamento farmacológico , Psicotrópicos/farmacologia , Interações Medicamentosas , Etanol/efeitos adversos , Etanol/farmacologia , Humanos , Hipertensão/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Inibidores da Monoaminoxidase/efeitos adversos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Alcaloides Opiáceos/efeitos adversos , Alcaloides Opiáceos/farmacologia , Alcaloides Opiáceos/uso terapêutico , Psicotrópicos/uso terapêutico , Síndrome da Serotonina/induzido quimicamente , Discinesia Tardia/induzido quimicamente
14.
J Clin Endocrinol Metab ; 104(10): 4619-4625, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265070

RESUMO

CONTEXT: The effect of antidepressant (ATD) use on mortality in patients with diabetes mellitus (DM) has not yet been sufficiently studied, although comorbid depression is common in this population. OBJECTIVE: To explore the impact of ATDs on mortality among DM patients. DESIGN: A retrospective cohort study in a national database. SETTING: This population-based study used the National Health Insurance Research Database in Taiwan. Since 2000, we identified 53,412 cases of newly diagnosed patients with DM and depression. Patient cases were followed for assessing mortality until 2013. MAIN OUTCOME MEASURE: The association between mortality and ATD use was explored adjusting for cumulative dosing. RESULTS: Using the time-dependent Cox regression model, ATD use was associated with significantly reduced mortality among patients with DM [in the highest dose group: hazard ratio (HR), 0.65; 95% CI, 0.59 to 0.71]. Further analysis showed that differences in mortality existed across ATD categories: selective serotonin reuptake inhibitors (HR, 0.63; 95% CI, 0.56 to 0.71), serotonin-norepinephrine reuptake inhibitors (HR, 0.58; 95% CI, 0.44 to 0.78), norepinephrine-dopamine reuptake inhibitors (HR, 0.20; 95% CI, 0.07 to 0.63), mirtazapine (HR, 0.60; 95% CI, 0.45 to 0.82), tricyclic/tetracyclic antidepressants (HR, 0.73; 95% CI, 0.54 to 0.97), and trazodone (HR, 0.52; 95% CI, 0.29 to 0.91). However, reversible inhibitor of monoamine oxidase A (RIMA) was found to be associated with an increase, rather than a decrease, in total mortality (HR, 1.48; 95% CI, 1.09 to 1.99). CONCLUSION: Most ATDs, but not RIMA, were associated with significantly reduced mortality among a population with comorbid DM and depression.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Mortalidade , Adolescente , Adulto , Idoso , Antidepressivos Tricíclicos/uso terapêutico , Estudos de Coortes , Comorbidade , Transtorno Depressivo/epidemiologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Inibidores da Captação de Dopamina/uso terapêutico , Transtorno Distímico/tratamento farmacológico , Transtorno Distímico/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Modelos de Riscos Proporcionais , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Taiwan/epidemiologia , Trazodona/uso terapêutico , Adulto Jovem
15.
Drugs Aging ; 36(9): 807-821, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31161581

RESUMO

Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico
16.
Ideggyogy Sz ; 72(5-6): 187-193, 2019 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31241263

RESUMO

Background and purpose: There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson's disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson's disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods: In our study we investigated the data of all Parkinson's patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists' usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: During the studied period a total of 2379 patients with Parkinson's disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson's disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion: The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.


Assuntos
Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Estudos Transversais , Humanos , Resultado do Tratamento
17.
Clin Neuropharmacol ; 42(4): 123-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31045589

RESUMO

OBJECTIVES: The aim of this open-label study was to investigate the long-term safety and efficacy of selegiline as monotherapy in Japanese patients with early Parkinson disease (PD). METHODS: We conducted a 56-week prospective study in patients with early PD (N = 134) who had previously completed the randomized, double-blind, placebo-controlled phase III trial of selegiline monotherapy for 12 weeks. In the present study, dosing was titrated from 2.5 to 10 mg/d in increments of 2.5 mg/d for 2 weeks. From the seventh week, the dosage was maintained at 10 mg/d until week 56. The primary outcome was any change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score (part I + II + III) from baseline. Secondary outcomes, including changes in the UPDRS subscores and safety profile, were also evaluated. RESULTS: Ninety-one (67.9%) patients completed the 56-week study. Treatment with selegiline significantly reduced total UPDRS score from week 4 (mean ± SD, -2.62 ± 3.83; P < 0.0001) to week 56 (-3.39 ± 9.27; P < 0.01). The peak effect was seen at week 20 (-5.79 ± 5.57; P < 0.0001). In addition, we found similar improvements in the UPDRS parts II and III scores. The incidence rate of adverse drug reactions was 44.3% (58 patients) and did not increase during the period of 10 mg selegiline administration. CONCLUSIONS: Long-term monotherapy with selegiline (10 mg/d) was effective and well tolerated in patients with early PD in this 56-week study.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Selegilina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Escala de Avaliação Comportamental , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Estudos Prospectivos , Selegilina/administração & dosagem
18.
Expert Opin Pharmacother ; 20(11): 1351-1363, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31120798

RESUMO

INTRODUCTION: Depression is a common non-motor symptom in Parkinson disease (PD), occurring in approximately 20% of patients with PD. While depression can occur anytime in the disease process, it predates PD diagnosis in about 30% of patients. Between 20% and 60% of depressed patients with PD are either without recognition or treatment of their depression. AREAS COVERED: The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon. EXPERT OPINION: Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Doença de Parkinson/patologia , Biomarcadores/metabolismo , Citocinas/metabolismo , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/etiologia , Exercício Físico , Humanos , Inibidores da Monoaminoxidase/uso terapêutico , Neurotransmissores/metabolismo , Doença de Parkinson/complicações , Inibidores de Captação de Serotonina/uso terapêutico
19.
Molecules ; 24(10)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130597

RESUMO

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I-IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects of two potent and selective Monoamine Oxidase B (MAO-B) inhibitors, Cmp3 and Cmp5, in C6 glioma cells and in CTX/TNA2 astrocytes in terms of cell proliferation, apoptosis occurrence, inflammatory events and cell migration. These compounds decrease C6 glioma cells viability sparing normal astrocytes. Cell cycle analysis, the Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) production were detected, revealing that Cmp3 and Cmp5 induce a G1 or G2/M cell cycle arrest, as well as a MMP depolarization and an overproduction of ROS; moreover, they inhibit the expression level of inducible nitric oxide synthase 2, thus contributing to fatal drug-induced oxidative stress. Cmp5 notably reduces glioma cell migration via down-regulating Matrix Metalloproteinases 2 and 9. This study demonstrated that our novel MAO-B inhibitors increase the oxidative stress level resulting in a cell cycle arrest and markedly reduces glioma cells migration thus reinforcing the hypothesis of a critical role-played by MAO-B in mediating oncogenesis in high-grade gliomas.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Citometria de Fluxo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Monoaminoxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
20.
Pak J Pharm Sci ; 32(1(Special)): 371-375, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852472

RESUMO

The present study designed to investigate the effect of monoamine oxidase inhibitor in the rat model of Coronary heart disease (cardiac hypertrophy). A total of 40 male adult Wistar rats having body weight 300-400 gram were equally distributed in two groups (Test group: Rats with Angiotensin II + monoamine oxidase inhibitor (Befloxatone); Reference group: Rats with cardiac hypertrophy induced by Angiotensin II). Rat model of cardiac hypertrophy were induced by Angiotensin II. Effect of Befloxatone on cardiac hypertrophy was evaluated by electrocardiography, hemodynamic and histological assessment. Vital signs such as pulse rate, and blood pressure were measured. Echocardiographic related variable including ejection fraction were also assessed in both the groups. Also, expression of monoamine oxidase was analyzed using by real-time-PCR and Western blot analysis. In results, we found following 1) monoamine oxidase inhibitor treatment prevents Angiotensin II induced increase in level of ANP and ßeta-myosin, which are responsible for inducing cardiac hypertrophic responses; 2) monoamine oxidase inhibitor ameliorates Angiotensin II induced cell enlargement by reducing the surface area of cells; 3) monoamine oxidase inhibitor attenuates the hypertrophic response triggered by Angiotensin II; 4) monoamine oxidase inhibitor ameliorates increased heart rate and average arterial pressure induced by angiotensin II; 5) Overall finding suggested that monoamine oxidase inhibitor improves left ventricle hypertrophy and ejection fraction by inhibiting monoamine oxidase enzyme in heart. The finding of this study gives the new vision to cardiovascular researchers to develop anti- hypertrophy therapy based on monoamine oxidase inhibition.


Assuntos
Cardiomegalia/tratamento farmacológico , Inibidores da Monoaminoxidase/uso terapêutico , Oxazóis/uso terapêutico , Angiotensina II , Animais , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Inibidores da Monoaminoxidase/administração & dosagem , Miocárdio/patologia , Oxazóis/administração & dosagem , Ratos Wistar
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